Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
The rate dynamics in chemical or physical systems.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
The sum of the weight of all the atoms in a molecule.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A prokaryotic ATP-dependent protease that plays a role in the degradation of many abnormal proteins. It is a tetramer of 87-kDa subunits, each of which contains a proteolytic site and a ATP-binding site.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.
Proteases that contain proteolytic core domains and ATPase-containing regulatory domains. They are usually comprised of large multi-subunit assemblies. The domains can occur within a single peptide chain or on distinct subunits.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The process of cleaving a chemical compound by the addition of a molecule of water.
Established cell cultures that have the potential to propagate indefinitely.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Proteins prepared by recombinant DNA technology.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Proteins found in any species of bacterium.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Elements of limited time intervals, contributing to particular results or situations.
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC
Multisubunit enzyme complexes that synthesize ADENOSINE TRIPHOSPHATE from energy sources such as ions traveling through channels.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation.
An ATP-dependent protease found in prokaryotes, CHLOROPLASTS, and MITOCHONDRIA. It is a soluble multisubunit complex that plays a role in the degradation of many abnormal proteins.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
Peptides composed of between two and twelve amino acids.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Transport proteins that carry specific substances in the blood or across cell membranes.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Physiologically inactive substances that can be converted to active enzymes.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC
Proton-translocating ATPases responsible for ADENOSINE TRIPHOSPHATE synthesis in the MITOCHONDRIA. They derive energy from the respiratory chain-driven reactions that develop high concentrations of protons within the intermembranous space of the mitochondria.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

Enhanced mitochondrial biogenesis is associated with increased expression of the mitochondrial ATP-dependent Lon protease. (1/362)

Rats bearing the Zajdela hepatoma tumor and T3-treated hypothyroid rats were used to study the role of protein degradation in the process of mitochondrial biogenesis. It was shown that the activity, protein and mRNA levels of the ATP-dependent Lon protease increased in rapidly growing Zajdela hepatoma cells. The increase in the rate of mitochondrial biogenesis by thyroid hormone was similarly accompanied by enhanced expression of the Lon protease. The results imply that mitochondrial biogenesis in mammalian cells is, at least partially, regulated by the matrix Lon protease.  (+info)

A conserved domain in Escherichia coli Lon protease is involved in substrate discriminator activity. (2/362)

Lon protease of Escherichia coli regulates a diverse set of physiological responses including cell division, capsule production, plasmid stability, and phage replication. Little is known about the mechanism of substrate recognition by Lon. To examine the interaction of Lon with two of its substrates, RcsA and SulA, we generated point mutations in lon which affected its substrate specificity. The most informative lon mutant overproduced capsular polysaccharide (RcsA stabilized) yet was resistant to DNA-damaging agents (SulA degraded). Immunoblots revealed that RcsA protein persisted in this mutant whereas SulA protein was rapidly degraded. The mutant contains a single-base change within lon leading to a single amino acid change of glutamate 240 to lysine. E240 is conserved among all Lon isolates and resides in a charged domain that has a high probability of adopting a coiled-coil conformation. This conformation, implicated in mediating protein-protein interactions, appears to confer substrate discriminator activity on Lon. We propose a model suggesting that this coiled-coil domain represents the discriminator site of Lon.  (+info)

Expression of mitochondrial marker proteins during spermatogenesis. (3/362)

Spermatogenesis is a highly complex, hormonally regulated cytodifferentiation process finally leading to the production of spermatozoa. In addition to other events germ cell differentiation is characterized by a gradual structural modification of many organelles including mitochondria which play a unique role. The morphological and functional development of germ cell mitochondria is a reflection of the permanent change in the testicular microenvironment which occurs when the germ cells are slowly moving from the base of the seminiferous epithelium to the lumen. Concomitant with the structural changes, several mitochondrial proteins are known to be expressed and synthesized during distinct phases of the organelle's development. This review pays particular attention to these transiently expressed mitochondrial proteins such as hsp60, Lon protease, sulphydryl oxidase and cytochrome ct. Furthermore, the biological function of this stepwise gene activation during mitochondrial and germ cell development is discussed.  (+info)

Substrate sequestration by a proteolytically inactive Lon mutant. (4/362)

Lon protein of Escherichia coli is an ATP-dependent protease responsible for the rapid turnover of both abnormal and naturally unstable proteins, including SulA, a cell division inhibitor made after DNA damage, and RcsA, a positive regulator of transcription. Lon is a multimer of identical 94-kDa subunits, each containing a consensus ATPase motif and a serine active site. We found that overexpressing Lon, which is mutated for the serine active site (LonS679A) and is therefore devoid of proteolytic activity, unexpectedly led to complementation of the UV sensitivity and capsule overproduction of a lon deletion mutant. SulA was not degraded by LonS679A, but rather was completely protected by the Lon mutant from degradation by other cellular proteases. We interpret these results to mean that the mutant LonS679A binds but does not degrade Lon substrates, resulting in sequestration of the substrate proteins and interference with their activities, resulting in apparent complementation. Lon that carried a mutation in the consensus ATPase site, either with or without the active site serine, was no longer able to complement a Deltalon mutant. These in vivo results suggest that the pathway of degradation by Lon couples ATP-dependent unfolding with movement of the substrate into protected chambers within Lon, where it is held until degradation proceeds. In the absence of degradation the substrate remains sequestered. Comparison of our results with those from a number of other systems suggest that proteins related to the regulatory portions of energy-dependent proteases act as energy-dependent sequestration proteins.  (+info)

Role of region C in regulation of the heat shock gene-specific sigma factor of Escherichia coli, sigma32. (5/362)

Expression of heat shock genes is controlled in Escherichia coli by the antagonistic action of the sigma32 subunit of RNA polymerase and the DnaK chaperone system, which inactivates sigma32 by stress-dependent association and mediates sigma32 degradation by the FtsH protease. A stretch of 23 residues (R122 to Q144) conserved among sigma32 homologs, termed region C, was proposed to play a role in sigma32 degradation, and peptide analysis identified two potential DnaK binding sites central and peripheral to region C. Region C is thus a prime candidate for mediating stress control of sigma32, a hypothesis that we tested in the present study. A peptide comprising the central DnaK binding site was an excellent substrate for FtsH, while a peptide comprising the peripheral DnaK binding site was a poor substrate. Replacement of a single hydrophobic residue in each DnaK binding site by negatively charged residues (I123D and F137E) strongly decreased the binding of the peptides to DnaK and the degradation by FtsH. However, introduction of these and additional region C alterations into the sigma32 protein did not affect sigma32 degradation in vivo and in vitro or DnaK binding in vitro. These findings do not support a role for region C in sigma32 control by DnaK and FtsH. Instead, the sigma32 mutants had reduced affinities for RNA polymerase and decreased transcriptional activities in vitro and in vivo. Furthermore, cysteines inserted into region C allowed cysteine-specific cross-linking of sigma32 to RNA polymerase. Region C thus confers on sigma32 a competitive advantage over other sigma factors to bind RNA polymerase and thereby contributes to the rapidity of the heat shock response.  (+info)

Dislocation of membrane proteins in FtsH-mediated proteolysis. (6/362)

Escherichia coli FtsH degrades several integral membrane proteins, including YccA, having seven transmembrane segments, a cytosolic N-terminus and a periplasmic C-terminus. Evidence indicates that FtsH initiates proteolysis at the N-terminal cytosolic domain. SecY, having 10 transmembrane segments, is also a substrate of FtsH. We studied whether and how the FtsH-catalyzed proteolysis on the cytosolic side continues into the transmembrane and periplasmic regions using chimeric proteins, YccA-(P3)-PhoA-His6-Myc and SecY-(P5)-PhoA, with the alkaline phosphatase (PhoA) mature sequence in a periplasmic domain. The PhoA domain that was present within the fusion protein was rapidly degraded by FtsH when it lacked the DsbA-dependent folding. In contrast, both PhoA itself and the TM9-PhoA region of SecY-(P5)-PhoA were stable when expressed as independent polypeptides. In the presence of DsbA, the FtsH-dependent degradation stopped at a site near to the N-terminus of the PhoA moiety, leaving the PhoA domain (and its C-terminal region) undigested. The efficiency of this degradation stop correlated well with the rapidity of the folding of the PhoA domain. Thus, both transmembrane and periplasmic domains are degraded by the processive proteolysis by FtsH, provided they are not tightly folded. We propose that FtsH dislocates the extracytoplasmic domain of a substrate, probably using its ATPase activity.  (+info)

Lon and Clp family proteases and chaperones share homologous substrate-recognition domains. (7/362)

Lon protease and members of the Clp family of molecular chaperones and protease regulatory subunits contain homologous regions with properties expected for substrate-binding domains. Fragments corresponding to these sequences are stably and independently folded for Lon, ClpA, and ClpY. The corresponding regions from ClpB and ClpX are unstable. All five fragments exhibit distinct patterns of binding to three proteins that are protease substrates in vivo: the heat shock transcription factor sigma32, the SOS mutagenesis protein UmuD, and Arc repressor bearing the SsrA degradation tag. Recognition of UmuD is mediated through peptide sequences within a 24-residue N-terminal region whereas recognition of both sigma32 and SsrA-tagged Arc requires sequences at the C terminus. These results indicate that the Lon and Clp proteases use the same mechanism of substrate discrimination and suggest that these related ATP-dependent bacterial proteases scrutinize accessible or disordered regions of potential substrates for the presence of specific targeting sequences.  (+info)

Mitochondrial Lon of Saccharomyces cerevisiae is a ring-shaped protease with seven flexible subunits. (8/362)

Lon (or La) is a soluble, homooligomeric ATP-dependent protease. Mass determination and cryoelectron microscopy of pure mitochondrial Lon from Saccharomyces cerevisiae identify Lon as a flexible ring-shaped heptamer. In the presence of ATP or 5'-adenylylimidodiphosphate, most of the rings are symmetric and resemble other ATP-driven machines that mediate folding and degradation of proteins. In the absence of nucleotides, most of the rings are distorted, with two adjacent subunits forming leg-like protrusions. These results suggest that asymmetric conformational changes serve to power processive unfolding and translocation of substrates to the active site of the Lon protease.  (+info)

Calpains are a family of calcium-dependent cysteine proteases that play important roles in various cellular processes, including signal transduction, cell death, and remodeling of the cytoskeleton. They are present in most tissues and can be activated by an increase in intracellular calcium levels. There are at least 15 different calpain isoforms identified in humans, which are categorized into two groups based on their calcium requirements for activation: classical calpains (calpain-1 and calpain-2) and non-classical calpains (calpain-3 to calpain-15). Dysregulation of calpain activity has been implicated in several pathological conditions, such as neurodegenerative diseases, muscular dystrophies, and cancer.

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

Adenosine triphosphatases (ATPases) are a group of enzymes that catalyze the conversion of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and inorganic phosphate. This reaction releases energy, which is used to drive various cellular processes such as muscle contraction, transport of ions across membranes, and synthesis of proteins and nucleic acids.

ATPases are classified into several types based on their structure, function, and mechanism of action. Some examples include:

1. P-type ATPases: These ATPases form a phosphorylated intermediate during the reaction cycle and are involved in the transport of ions across membranes, such as the sodium-potassium pump and calcium pumps.
2. F-type ATPases: These ATPases are found in mitochondria, chloroplasts, and bacteria, and are responsible for generating a proton gradient across the membrane, which is used to synthesize ATP.
3. V-type ATPases: These ATPases are found in vacuolar membranes and endomembranes, and are involved in acidification of intracellular compartments.
4. A-type ATPases: These ATPases are found in the plasma membrane and are involved in various functions such as cell signaling and ion transport.

Overall, ATPases play a crucial role in maintaining the energy balance of cells and regulating various physiological processes.

Endopeptidases are a type of enzyme that breaks down proteins by cleaving peptide bonds inside the polypeptide chain. They are also known as proteinases or endoproteinases. These enzymes work within the interior of the protein molecule, cutting it at specific points along its length, as opposed to exopeptidases, which remove individual amino acids from the ends of the protein chain.

Endopeptidases play a crucial role in various biological processes, such as digestion, blood coagulation, and programmed cell death (apoptosis). They are classified based on their catalytic mechanism and the structure of their active site. Some examples of endopeptidase families include serine proteases, cysteine proteases, aspartic proteases, and metalloproteases.

It is important to note that while endopeptidases are essential for normal physiological functions, they can also contribute to disease processes when their activity is unregulated or misdirected. For instance, excessive endopeptidase activity has been implicated in the pathogenesis of neurodegenerative disorders, cancer, and inflammatory conditions.

Peptide hydrolases, also known as proteases or peptidases, are a group of enzymes that catalyze the hydrolysis of peptide bonds in proteins and peptides. They play a crucial role in various biological processes such as protein degradation, digestion, cell signaling, and regulation of various physiological functions. Based on their catalytic mechanism and the specificity for the peptide bond, they are classified into several types, including serine proteases, cysteine proteases, aspartic proteases, and metalloproteases. These enzymes have important clinical applications in the diagnosis and treatment of various diseases, such as cancer, viral infections, and inflammatory disorders.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Blood platelets, also known as thrombocytes, are small, colorless cell fragments in our blood that play an essential role in normal blood clotting. They are formed in the bone marrow from large cells called megakaryocytes and circulate in the blood in an inactive state until they are needed to help stop bleeding. When a blood vessel is damaged, platelets become activated and change shape, releasing chemicals that attract more platelets to the site of injury. These activated platelets then stick together to form a plug, or clot, that seals the wound and prevents further blood loss. In addition to their role in clotting, platelets also help to promote healing by releasing growth factors that stimulate the growth of new tissue.

Molecular weight, also known as molecular mass, is the mass of a molecule. It is expressed in units of atomic mass units (amu) or daltons (Da). Molecular weight is calculated by adding up the atomic weights of each atom in a molecule. It is a useful property in chemistry and biology, as it can be used to determine the concentration of a substance in a solution, or to calculate the amount of a substance that will react with another in a chemical reaction.

Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.

In this process:

1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.

EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Protease inhibitors are a class of antiviral drugs that are used to treat infections caused by retroviruses, such as the human immunodeficiency virus (HIV), which is responsible for causing AIDS. These drugs work by blocking the activity of protease enzymes, which are necessary for the replication and multiplication of the virus within infected cells.

Protease enzymes play a crucial role in the life cycle of retroviruses by cleaving viral polyproteins into functional units that are required for the assembly of new viral particles. By inhibiting the activity of these enzymes, protease inhibitors prevent the virus from replicating and spreading to other cells, thereby slowing down the progression of the infection.

Protease inhibitors are often used in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS. Common examples of protease inhibitors include saquinavir, ritonavir, indinavir, and atazanavir. While these drugs have been successful in improving the outcomes of people living with HIV/AIDS, they can also cause side effects such as nausea, diarrhea, headaches, and lipodystrophy (changes in body fat distribution).

HIV Protease is a crucial enzyme that plays a significant role in the replication cycle of the Human Immunodeficiency Virus (HIV). It is responsible for cleaving or cutting specific long protein chains, produced during the translation of viral RNA, into smaller functional proteins. These proteins are essential for the formation of new virus particles.

The HIV Protease enzyme functions like a pair of molecular scissors, recognizing and cutting particular amino acid sequences in these polyprotein chains. By inhibiting this enzyme's activity with antiretroviral drugs known as protease inhibitors, the production of mature, infectious viral particles can be effectively prevented, which is a crucial component of highly active antiretroviral therapy (HAART) for managing HIV infection and reducing the risk of transmitting the virus to others.

Serine endopeptidases are a type of enzymes that cleave peptide bonds within proteins (endopeptidases) and utilize serine as the nucleophilic amino acid in their active site for catalysis. These enzymes play crucial roles in various biological processes, including digestion, blood coagulation, and programmed cell death (apoptosis). Examples of serine endopeptidases include trypsin, chymotrypsin, thrombin, and elastase.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

I'm sorry for any confusion, but "Protease La" doesn't seem to be a standard term in medicine or biochemistry. It's possible that there might be a misunderstanding or a typo in the term. Proteases are enzymes that break down proteins into smaller peptides or individual amino acids. If you have more context or if you meant a different term, please provide additional information so I can give a more accurate response.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Cysteine proteases are a type of enzymes that cleave peptide bonds in proteins, and they require a cysteine residue in their active site to do so. These enzymes play important roles in various biological processes, including protein degradation, cell signaling, and inflammation. They can be found in various tissues and organisms, including humans, where they are involved in many physiological and pathological conditions.

Cysteine proteases are characterized by a conserved catalytic mechanism that involves a nucleophilic attack on the peptide bond carbonyl carbon by the thiolate anion of the cysteine residue, resulting in the formation of an acyl-enzyme intermediate. This intermediate is then hydrolyzed to release the cleaved protein fragments.

Some examples of cysteine proteases include cathepsins, caspases, and calpains, which are involved in various cellular processes such as apoptosis, autophagy, and signal transduction. Dysregulation of these enzymes has been implicated in several diseases, including cancer, neurodegenerative disorders, and infectious diseases. Therefore, cysteine proteases have emerged as important therapeutic targets for the development of new drugs to treat these conditions.

ATP-dependent proteases are a type of protein complex that play a crucial role in maintaining cellular homeostasis by breaking down damaged or misfolded proteins. They use the energy from ATP (adenosine triphosphate) hydrolysis to unfold and degrade these proteins into smaller peptides or individual amino acids, which can then be recycled or disposed of by the cell.

These proteases are essential for a variety of cellular processes, including protein quality control, regulation of cell signaling pathways, and clearance of damaged organelles. They are also involved in various cellular responses to stress, such as the unfolded protein response (UPR) and autophagy.

There are several different types of ATP-dependent proteases, including the 26S proteasome, which is responsible for degrading most intracellular proteins, and the Clp/Hsp100 family of proteases, which are involved in protein folding and disaggregation. Dysregulation of ATP-dependent proteases has been implicated in various diseases, including neurodegenerative disorders, cancer, and infectious diseases.

Cysteine endopeptidases are a type of enzymes that cleave peptide bonds within proteins. They are also known as cysteine proteases or cysteine proteinases. These enzymes contain a catalytic triad consisting of three amino acids: cysteine, histidine, and aspartate. The thiol group (-SH) of the cysteine residue acts as a nucleophile and attacks the carbonyl carbon of the peptide bond, leading to its cleavage.

Cysteine endopeptidases play important roles in various biological processes, including protein degradation, cell signaling, and inflammation. They are involved in many physiological and pathological conditions, such as apoptosis, immune response, and cancer. Some examples of cysteine endopeptidases include cathepsins, caspases, and calpains.

It is important to note that these enzymes require a reducing environment to maintain the reduced state of their active site cysteine residue. Therefore, they are sensitive to oxidizing agents and inhibitors that target the thiol group. Understanding the structure and function of cysteine endopeptidases is crucial for developing therapeutic strategies that target these enzymes in various diseases.

Protease nexins are a group of proteins that regulate the activity of proteases, which are enzymes that break down other proteins. Proteases play important roles in various biological processes, including blood clotting, immune response, and cell death. However, uncontrolled or excessive protease activity can lead to harmful effects, such as tissue damage and disease progression.

Protease nexins function by forming stable complexes with specific proteases, thereby inhibiting their activity. These complexes also serve as a reservoir of inactive proteases that can be rapidly activated when needed. Protease nexins are involved in various physiological and pathological processes, such as inflammation, neurodegeneration, and cancer.

One well-known example of a protease nexin is the tissue plasminogen activator (tPA) - neuroserpin complex. Neuroserpin is a serine protease inhibitor that forms a complex with tPA, an enzyme that plays a critical role in breaking down blood clots. By forming this complex, neuroserpin regulates the activity of tPA and prevents excessive fibrinolysis, which can lead to bleeding disorders. Mutations in the gene encoding neuroserpin have been associated with familial dementia with Lewy bodies, a form of neurodegenerative disorder.

Serine proteinase inhibitors, also known as serine protease inhibitors or serpins, are a group of proteins that inhibit serine proteases, which are enzymes that cut other proteins in a process called proteolysis. Serine proteinases are important in many biological processes such as blood coagulation, fibrinolysis, inflammation and cell death. The inhibition of these enzymes by serpin proteins is an essential regulatory mechanism to maintain the balance and prevent uncontrolled proteolytic activity that can lead to diseases.

Serpins work by forming a covalent complex with their target serine proteinases, irreversibly inactivating them. The active site of serpins contains a reactive center loop (RCL) that mimics the protease's target protein sequence and acts as a bait for the enzyme. When the protease cleaves the RCL, it gets trapped within the serpin structure, leading to its inactivation.

Serpin proteinase inhibitors play crucial roles in various physiological processes, including:

1. Blood coagulation and fibrinolysis regulation: Serpins such as antithrombin, heparin cofactor II, and protease nexin-2 control the activity of enzymes involved in blood clotting and dissolution to prevent excessive or insufficient clot formation.
2. Inflammation modulation: Serpins like α1-antitrypsin, α2-macroglobulin, and C1 inhibitor regulate the activity of proteases released during inflammation, protecting tissues from damage.
3. Cell death regulation: Some serpins, such as PI-9/SERPINB9, control apoptosis (programmed cell death) by inhibiting granzyme B, a protease involved in this process.
4. Embryonic development and tissue remodeling: Serpins like plasminogen activator inhibitor-1 (PAI-1) and PAI-2 regulate the activity of enzymes involved in extracellular matrix degradation during embryonic development and tissue remodeling.
5. Neuroprotection: Serpins such as neuroserpin protect neurons from damage by inhibiting proteases released during neuroinflammation or neurodegenerative diseases.

Dysregulation of serpins has been implicated in various pathological conditions, including thrombosis, emphysema, Alzheimer's disease, and cancer. Understanding the roles of serpins in these processes may provide insights into potential therapeutic strategies for treating these diseases.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

Hydrolysis is a chemical process, not a medical one. However, it is relevant to medicine and biology.

Hydrolysis is the breakdown of a chemical compound due to its reaction with water, often resulting in the formation of two or more simpler compounds. In the context of physiology and medicine, hydrolysis is a crucial process in various biological reactions, such as the digestion of food molecules like proteins, carbohydrates, and fats. Enzymes called hydrolases catalyze these hydrolysis reactions to speed up the breakdown process in the body.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

'Escherichia coli' (E. coli) is a type of gram-negative, facultatively anaerobic, rod-shaped bacterium that commonly inhabits the intestinal tract of humans and warm-blooded animals. It is a member of the family Enterobacteriaceae and one of the most well-studied prokaryotic model organisms in molecular biology.

While most E. coli strains are harmless and even beneficial to their hosts, some serotypes can cause various forms of gastrointestinal and extraintestinal illnesses in humans and animals. These pathogenic strains possess virulence factors that enable them to colonize and damage host tissues, leading to diseases such as diarrhea, urinary tract infections, pneumonia, and sepsis.

E. coli is a versatile organism with remarkable genetic diversity, which allows it to adapt to various environmental niches. It can be found in water, soil, food, and various man-made environments, making it an essential indicator of fecal contamination and a common cause of foodborne illnesses. The study of E. coli has contributed significantly to our understanding of fundamental biological processes, including DNA replication, gene regulation, and protein synthesis.

Hydrogen-ion concentration, also known as pH, is a measure of the acidity or basicity of a solution. It is defined as the negative logarithm (to the base 10) of the hydrogen ion activity in a solution. The standard unit of measurement is the pH unit. A pH of 7 is neutral, less than 7 is acidic, and greater than 7 is basic.

In medical terms, hydrogen-ion concentration is important for maintaining homeostasis within the body. For example, in the stomach, a high hydrogen-ion concentration (low pH) is necessary for the digestion of food. However, in other parts of the body such as blood, a high hydrogen-ion concentration can be harmful and lead to acidosis. Conversely, a low hydrogen-ion concentration (high pH) in the blood can lead to alkalosis. Both acidosis and alkalosis can have serious consequences on various organ systems if not corrected.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Bacterial proteins are a type of protein that are produced by bacteria as part of their structural or functional components. These proteins can be involved in various cellular processes, such as metabolism, DNA replication, transcription, and translation. They can also play a role in bacterial pathogenesis, helping the bacteria to evade the host's immune system, acquire nutrients, and multiply within the host.

Bacterial proteins can be classified into different categories based on their function, such as:

1. Enzymes: Proteins that catalyze chemical reactions in the bacterial cell.
2. Structural proteins: Proteins that provide structural support and maintain the shape of the bacterial cell.
3. Signaling proteins: Proteins that help bacteria to communicate with each other and coordinate their behavior.
4. Transport proteins: Proteins that facilitate the movement of molecules across the bacterial cell membrane.
5. Toxins: Proteins that are produced by pathogenic bacteria to damage host cells and promote infection.
6. Surface proteins: Proteins that are located on the surface of the bacterial cell and interact with the environment or host cells.

Understanding the structure and function of bacterial proteins is important for developing new antibiotics, vaccines, and other therapeutic strategies to combat bacterial infections.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

Cysteine proteinase inhibitors are a type of molecule that bind to and inhibit the activity of cysteine proteases, which are enzymes that cleave proteins at specific sites containing the amino acid cysteine. These inhibitors play important roles in regulating various biological processes, including inflammation, immune response, and programmed cell death (apoptosis). They can also have potential therapeutic applications in diseases where excessive protease activity contributes to pathology, such as cancer, arthritis, and neurodegenerative disorders. Examples of cysteine proteinase inhibitors include cystatins, kininogens, and serpins.

Sequence homology, amino acid, refers to the similarity in the order of amino acids in a protein or a portion of a protein between two or more species. This similarity can be used to infer evolutionary relationships and functional similarities between proteins. The higher the degree of sequence homology, the more likely it is that the proteins are related and have similar functions. Sequence homology can be determined through various methods such as pairwise alignment or multiple sequence alignment, which compare the sequences and calculate a score based on the number and type of matching amino acids.

Cathepsins are a type of proteolytic enzymes, which are found in lysosomes and are responsible for breaking down proteins inside the cell. They are classified as papain-like cysteine proteases and play important roles in various physiological processes, including tissue remodeling, antigen presentation, and apoptosis (programmed cell death). There are several different types of cathepsins, including cathepsin B, C, D, F, H, K, L, S, V, and X/Z, each with distinct substrate specificities and functions.

Dysregulation of cathepsins has been implicated in various pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders. For example, overexpression or hyperactivation of certain cathepsins has been shown to contribute to tumor invasion and metastasis, while their inhibition has been explored as a potential therapeutic strategy in cancer treatment. Similarly, abnormal levels of cathepsins have been linked to the progression of neurodegenerative diseases like Alzheimer's and Parkinson's, making them attractive targets for drug development.

Adenosine diphosphate (ADP) is a chemical compound that plays a crucial role in energy transfer within cells. It is a nucleotide, which consists of a adenosine molecule (a sugar molecule called ribose attached to a nitrogenous base called adenine) and two phosphate groups.

In the cell, ADP functions as an intermediate in the conversion of energy from one form to another. When a high-energy phosphate bond in ADP is broken, energy is released and ADP is converted to adenosine triphosphate (ATP), which serves as the main energy currency of the cell. Conversely, when ATP donates a phosphate group to another molecule, it is converted back to ADP, releasing energy for the cell to use.

ADP also plays a role in blood clotting and other physiological processes. In the coagulation cascade, ADP released from damaged red blood cells can help activate platelets and initiate the formation of a blood clot.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Trypsin is a proteolytic enzyme, specifically a serine protease, that is secreted by the pancreas as an inactive precursor, trypsinogen. Trypsinogen is converted into its active form, trypsin, in the small intestine by enterokinase, which is produced by the intestinal mucosa.

Trypsin plays a crucial role in digestion by cleaving proteins into smaller peptides at specific arginine and lysine residues. This enzyme helps to break down dietary proteins into amino acids, allowing for their absorption and utilization by the body. Additionally, trypsin can activate other zymogenic pancreatic enzymes, such as chymotrypsinogen and procarboxypeptidases, thereby contributing to overall protein digestion.

ATP synthetase complexes are molecular machines found in the inner membrane of mitochondria and the bacterial cell membrane that catalyze the synthesis of Adenosine Triphosphate (ATP) from ADP and inorganic phosphate. They are also known as F1F0-ATPases or complex V of the electron transport chain.

The complex is composed of two main parts: the F1 portion, which is located on the matrix side of the inner mitochondrial membrane and contains the catalytic site for ATP synthesis; and the F0 portion, which is embedded in the membrane and acts as a proton channel.

The process of ATP synthesis is coupled to the flow of protons across the membrane, driven by the electrochemical gradient generated by the electron transport chain. As protons flow through the F0 portion, they cause the F1 portion to rotate, which in turn drives the synthesis of ATP from ADP and Pi at the catalytic site.

ATP synthetase complexes are essential for cellular energy production and are conserved across all kingdoms of life.

Post-translational protein processing refers to the modifications and changes that proteins undergo after their synthesis on ribosomes, which are complex molecular machines responsible for protein synthesis. These modifications occur through various biochemical processes and play a crucial role in determining the final structure, function, and stability of the protein.

The process begins with the translation of messenger RNA (mRNA) into a linear polypeptide chain, which is then subjected to several post-translational modifications. These modifications can include:

1. Proteolytic cleavage: The removal of specific segments or domains from the polypeptide chain by proteases, resulting in the formation of mature, functional protein subunits.
2. Chemical modifications: Addition or modification of chemical groups to the side chains of amino acids, such as phosphorylation (addition of a phosphate group), glycosylation (addition of sugar moieties), methylation (addition of a methyl group), acetylation (addition of an acetyl group), and ubiquitination (addition of a ubiquitin protein).
3. Disulfide bond formation: The oxidation of specific cysteine residues within the polypeptide chain, leading to the formation of disulfide bonds between them. This process helps stabilize the three-dimensional structure of proteins, particularly in extracellular environments.
4. Folding and assembly: The acquisition of a specific three-dimensional conformation by the polypeptide chain, which is essential for its function. Chaperone proteins assist in this process to ensure proper folding and prevent aggregation.
5. Protein targeting: The directed transport of proteins to their appropriate cellular locations, such as the nucleus, mitochondria, endoplasmic reticulum, or plasma membrane. This is often facilitated by specific signal sequences within the protein that are recognized and bound by transport machinery.

Collectively, these post-translational modifications contribute to the functional diversity of proteins in living organisms, allowing them to perform a wide range of cellular processes, including signaling, catalysis, regulation, and structural support.

Ubiquitin-specific proteases (USPs) are a type of deubiquitinating enzymes (DUBs) that specifically cleave ubiquitin from proteins. Ubiquitination is a post-translational modification in which ubiquitin molecules are attached to proteins, targeting them for degradation by the proteasome. USPs reverse this process by removing ubiquitin molecules from proteins, thereby regulating protein stability, localization, and activity.

USPs contain a conserved catalytic domain that is responsible for the deubiquitinating activity. They are involved in various cellular processes, including DNA damage repair, gene expression regulation, inflammation, and immune response. Dysregulation of USP function has been implicated in several diseases, such as cancer, neurodegenerative disorders, and viral infections. Therefore, USPs are considered potential therapeutic targets for the development of drugs to treat these conditions.

Endopeptidase Clp is a type of enzyme found in bacteria that functions to degrade misfolded or unnecessary proteins within the cell. It is part of the ATP-dependent Clp protease family, which are complexes composed of multiple subunits, including the endopeptidase ClpP. These enzymes work together to unfold and break down proteins into smaller peptides or individual amino acids for recycling or removal. Endopeptidase Clp specifically recognizes and cleaves internal peptide bonds within proteins, contributing to protein quality control and maintaining cellular homeostasis in bacteria.

Membrane proteins are a type of protein that are embedded in the lipid bilayer of biological membranes, such as the plasma membrane of cells or the inner membrane of mitochondria. These proteins play crucial roles in various cellular processes, including:

1. Cell-cell recognition and signaling
2. Transport of molecules across the membrane (selective permeability)
3. Enzymatic reactions at the membrane surface
4. Energy transduction and conversion
5. Mechanosensation and signal transduction

Membrane proteins can be classified into two main categories: integral membrane proteins, which are permanently associated with the lipid bilayer, and peripheral membrane proteins, which are temporarily or loosely attached to the membrane surface. Integral membrane proteins can further be divided into three subcategories based on their topology:

1. Transmembrane proteins, which span the entire width of the lipid bilayer with one or more alpha-helices or beta-barrels.
2. Lipid-anchored proteins, which are covalently attached to lipids in the membrane via a glycosylphosphatidylinositol (GPI) anchor or other lipid modifications.
3. Monotopic proteins, which are partially embedded in the membrane and have one or more domains exposed to either side of the bilayer.

Membrane proteins are essential for maintaining cellular homeostasis and are targets for various therapeutic interventions, including drug development and gene therapy. However, their structural complexity and hydrophobicity make them challenging to study using traditional biochemical methods, requiring specialized techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and single-particle cryo-electron microscopy (cryo-EM).

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Metalloendopeptidases are a type of enzymes that cleave peptide bonds in proteins, specifically at interior positions within the polypeptide chain. They require metal ions as cofactors for their catalytic activity, typically zinc (Zn2+) or cobalt (Co2+). These enzymes play important roles in various biological processes such as protein degradation, processing, and signaling. Examples of metalloendopeptidases include thermolysin, matrix metalloproteinases (MMPs), and neutrophil elastase.

Subtilisins are a group of serine proteases that are produced by certain bacteria, including Bacillus subtilis. They are named after the bacterium and the Latin word "subtilis," which means delicate or finely made. Subtilisins are alkaline proteases, meaning they work best in slightly basic conditions.

Subtilisins have a broad specificity for cleaving peptide bonds and can hydrolyze a wide range of protein substrates. They are widely used in industry for various applications such as detergents, food processing, leather treatment, and biotechnology due to their ability to function at high temperatures and in the presence of denaturing agents.

In medicine, subtilisins have been studied for their potential use in therapeutic applications, including as anti-inflammatory agents and in wound healing. However, more research is needed to fully understand their mechanisms of action and potential benefits.

A cell membrane, also known as the plasma membrane, is a thin semi-permeable phospholipid bilayer that surrounds all cells in animals, plants, and microorganisms. It functions as a barrier to control the movement of substances in and out of the cell, allowing necessary molecules such as nutrients, oxygen, and signaling molecules to enter while keeping out harmful substances and waste products. The cell membrane is composed mainly of phospholipids, which have hydrophilic (water-loving) heads and hydrophobic (water-fearing) tails. This unique structure allows the membrane to be flexible and fluid, yet selectively permeable. Additionally, various proteins are embedded in the membrane that serve as channels, pumps, receptors, and enzymes, contributing to the cell's overall functionality and communication with its environment.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Chymotrypsin is a proteolytic enzyme, specifically a serine protease, that is produced in the pancreas and secreted into the small intestine as an inactive precursor called chymotrypsinogen. Once activated, chymotrypsin helps to digest proteins in food by breaking down specific peptide bonds in protein molecules. Its activity is based on the recognition of large hydrophobic side chains in amino acids like phenylalanine, tryptophan, and tyrosine. Chymotrypsin plays a crucial role in maintaining normal digestion and absorption processes in the human body.

Oligopeptides are defined in medicine and biochemistry as short chains of amino acids, typically containing fewer than 20 amino acid residues. These small peptides are important components in various biological processes, such as serving as signaling molecules, enzyme inhibitors, or structural elements in some proteins. They can be found naturally in foods and may also be synthesized for use in medical research and therapeutic applications.

Biological models, also known as physiological models or organismal models, are simplified representations of biological systems, processes, or mechanisms that are used to understand and explain the underlying principles and relationships. These models can be theoretical (conceptual or mathematical) or physical (such as anatomical models, cell cultures, or animal models). They are widely used in biomedical research to study various phenomena, including disease pathophysiology, drug action, and therapeutic interventions.

Examples of biological models include:

1. Mathematical models: These use mathematical equations and formulas to describe complex biological systems or processes, such as population dynamics, metabolic pathways, or gene regulation networks. They can help predict the behavior of these systems under different conditions and test hypotheses about their underlying mechanisms.
2. Cell cultures: These are collections of cells grown in a controlled environment, typically in a laboratory dish or flask. They can be used to study cellular processes, such as signal transduction, gene expression, or metabolism, and to test the effects of drugs or other treatments on these processes.
3. Animal models: These are living organisms, usually vertebrates like mice, rats, or non-human primates, that are used to study various aspects of human biology and disease. They can provide valuable insights into the pathophysiology of diseases, the mechanisms of drug action, and the safety and efficacy of new therapies.
4. Anatomical models: These are physical representations of biological structures or systems, such as plastic models of organs or tissues, that can be used for educational purposes or to plan surgical procedures. They can also serve as a basis for developing more sophisticated models, such as computer simulations or 3D-printed replicas.

Overall, biological models play a crucial role in advancing our understanding of biology and medicine, helping to identify new targets for therapeutic intervention, develop novel drugs and treatments, and improve human health.

Aspartic acid endopeptidases are a type of enzyme that cleave peptide bonds within proteins. They are also known as aspartyl proteases or aspartic proteinases. These enzymes contain two catalytic aspartic acid residues in their active site, which work together to hydrolyze the peptide bond.

Aspartic acid endopeptidases play important roles in various biological processes, including protein degradation, processing, and activation. They are found in many organisms, including viruses, bacteria, fungi, plants, and animals. Some well-known examples of aspartic acid endopeptidases include pepsin, cathepsin D, and HIV protease.

Pepsin is a digestive enzyme found in the stomach that helps break down proteins in food. Cathepsin D is a lysosomal enzyme that plays a role in protein turnover and degradation within cells. HIV protease is an essential enzyme for the replication of the human immunodeficiency virus (HIV), which causes AIDS. Inhibitors of HIV protease are used as antiretroviral drugs to treat HIV infection.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Recombinant fusion proteins are artificially created biomolecules that combine the functional domains or properties of two or more different proteins into a single protein entity. They are generated through recombinant DNA technology, where the genes encoding the desired protein domains are linked together and expressed as a single, chimeric gene in a host organism, such as bacteria, yeast, or mammalian cells.

The resulting fusion protein retains the functional properties of its individual constituent proteins, allowing for novel applications in research, diagnostics, and therapeutics. For instance, recombinant fusion proteins can be designed to enhance protein stability, solubility, or immunogenicity, making them valuable tools for studying protein-protein interactions, developing targeted therapies, or generating vaccines against infectious diseases or cancer.

Examples of recombinant fusion proteins include:

1. Etaglunatide (ABT-523): A soluble Fc fusion protein that combines the heavy chain fragment crystallizable region (Fc) of an immunoglobulin with the extracellular domain of the human interleukin-6 receptor (IL-6R). This fusion protein functions as a decoy receptor, neutralizing IL-6 and its downstream signaling pathways in rheumatoid arthritis.
2. Etanercept (Enbrel): A soluble TNF receptor p75 Fc fusion protein that binds to tumor necrosis factor-alpha (TNF-α) and inhibits its proinflammatory activity, making it a valuable therapeutic option for treating autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis, and psoriasis.
3. Abatacept (Orencia): A fusion protein consisting of the extracellular domain of cytotoxic T-lymphocyte antigen 4 (CTLA-4) linked to the Fc region of an immunoglobulin, which downregulates T-cell activation and proliferation in autoimmune diseases like rheumatoid arthritis.
4. Belimumab (Benlysta): A monoclonal antibody that targets B-lymphocyte stimulator (BLyS) protein, preventing its interaction with the B-cell surface receptor and inhibiting B-cell activation in systemic lupus erythematosus (SLE).
5. Romiplostim (Nplate): A fusion protein consisting of a thrombopoietin receptor agonist peptide linked to an immunoglobulin Fc region, which stimulates platelet production in patients with chronic immune thrombocytopenia (ITP).
6. Darbepoetin alfa (Aranesp): A hyperglycosylated erythropoiesis-stimulating protein that functions as a longer-acting form of recombinant human erythropoietin, used to treat anemia in patients with chronic kidney disease or cancer.
7. Palivizumab (Synagis): A monoclonal antibody directed against the F protein of respiratory syncytial virus (RSV), which prevents RSV infection and is administered prophylactically to high-risk infants during the RSV season.
8. Ranibizumab (Lucentis): A recombinant humanized monoclonal antibody fragment that binds and inhibits vascular endothelial growth factor A (VEGF-A), used in the treatment of age-related macular degeneration, diabetic retinopathy, and other ocular disorders.
9. Cetuximab (Erbitux): A chimeric monoclonal antibody that binds to epidermal growth factor receptor (EGFR), used in the treatment of colorectal cancer and head and neck squamous cell carcinoma.
10. Adalimumab (Humira): A fully humanized monoclonal antibody that targets tumor necrosis factor-alpha (TNF-α), used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriasis, and Crohn's disease.
11. Bevacizumab (Avastin): A recombinant humanized monoclonal antibody that binds to VEGF-A, used in the treatment of various cancers, including colorectal, lung, breast, and kidney cancer.
12. Trastuzumab (Herceptin): A humanized monoclonal antibody that targets HER2/neu receptor, used in the treatment of breast cancer.
13. Rituximab (Rituxan): A chimeric monoclonal antibody that binds to CD20 antigen on B cells, used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis.
14. Palivizumab (Synagis): A humanized monoclonal antibody that binds to the F protein of respiratory syncytial virus, used in the prevention of respiratory syncytial virus infection in high-risk infants.
15. Infliximab (Remicade): A chimeric monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis.
16. Natalizumab (Tysabri): A humanized monoclonal antibody that binds to α4β1 integrin, used in the treatment of multiple sclerosis and Crohn's disease.
17. Adalimumab (Humira): A fully human monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis.
18. Golimumab (Simponi): A fully human monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.
19. Certolizumab pegol (Cimzia): A PEGylated Fab' fragment of a humanized monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.
20. Ustekinumab (Stelara): A fully human monoclonal antibody that targets IL-12 and IL-23, used in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease.
21. Secukinumab (Cosentyx): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis.
22. Ixekizumab (Taltz): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis and psoriatic arthritis.
23. Brodalumab (Siliq): A fully human monoclonal antibody that targets IL-17 receptor A, used in the treatment of psoriasis.
24. Sarilumab (Kevzara): A fully human monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis.
25. Tocilizumab (Actemra): A humanized monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T-cell-induced cytokine release syndrome.
26. Siltuximab (Sylvant): A chimeric monoclonal antibody that targets IL-6, used in the treatment of multicentric Castleman disease.
27. Satralizumab (Enspryng): A humanized monoclonal antibody that targets IL-6 receptor alpha, used in the treatment of neuromyelitis optica spectrum disorder.
28. Sirukumab (Plivensia): A human monoclonal antibody that targets IL-6, used in the treatment

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

A peptide fragment is a short chain of amino acids that is derived from a larger peptide or protein through various biological or chemical processes. These fragments can result from the natural breakdown of proteins in the body during regular physiological processes, such as digestion, or they can be produced experimentally in a laboratory setting for research or therapeutic purposes.

Peptide fragments are often used in research to map the structure and function of larger peptides and proteins, as well as to study their interactions with other molecules. In some cases, peptide fragments may also have biological activity of their own and can be developed into drugs or diagnostic tools. For example, certain peptide fragments derived from hormones or neurotransmitters may bind to receptors in the body and mimic or block the effects of the full-length molecule.

I believe there may be some confusion in your question. "Rabbits" is a common name used to refer to the Lagomorpha species, particularly members of the family Leporidae. They are small mammals known for their long ears, strong legs, and quick reproduction.

However, if you're referring to "rabbits" in a medical context, there is a term called "rabbit syndrome," which is a rare movement disorder characterized by repetitive, involuntary movements of the fingers, resembling those of a rabbit chewing. It is also known as "finger-chewing chorea." This condition is usually associated with certain medications, particularly antipsychotics, and typically resolves when the medication is stopped or adjusted.

Proteolysis is the biological process of breaking down proteins into smaller polypeptides or individual amino acids by the action of enzymes called proteases. This process is essential for various physiological functions, including digestion, protein catabolism, cell signaling, and regulation of numerous biological activities. Dysregulation of proteolysis can contribute to several pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders.

Site-directed mutagenesis is a molecular biology technique used to introduce specific and targeted changes to a specific DNA sequence. This process involves creating a new variant of a gene or a specific region of interest within a DNA molecule by introducing a planned, deliberate change, or mutation, at a predetermined site within the DNA sequence.

The methodology typically involves the use of molecular tools such as PCR (polymerase chain reaction), restriction enzymes, and/or ligases to introduce the desired mutation(s) into a plasmid or other vector containing the target DNA sequence. The resulting modified DNA molecule can then be used to transform host cells, allowing for the production of large quantities of the mutated gene or protein for further study.

Site-directed mutagenesis is a valuable tool in basic research, drug discovery, and biotechnology applications where specific changes to a DNA sequence are required to understand gene function, investigate protein structure/function relationships, or engineer novel biological properties into existing genes or proteins.

In genetics, sequence alignment is the process of arranging two or more DNA, RNA, or protein sequences to identify regions of similarity or homology between them. This is often done using computational methods to compare the nucleotide or amino acid sequences and identify matching patterns, which can provide insight into evolutionary relationships, functional domains, or potential genetic disorders. The alignment process typically involves adjusting gaps and mismatches in the sequences to maximize the similarity between them, resulting in an aligned sequence that can be visually represented and analyzed.

Pepstatins are a group of naturally occurring cyclic peptides that inhibit aspartic proteases, a type of enzyme that breaks down proteins. They are isolated from various actinomycete species of Streptomyces and Actinosynnema. Pepstatins are often used in laboratory research to study the function of aspartic proteases and as tools to probe the mechanism of action of these enzymes. In addition, pepstatins have been explored for their potential therapeutic use in various diseases, including cancer, viral infections, and cardiovascular disease. However, they have not yet been approved for clinical use.

Mitochondria are specialized structures located inside cells that convert the energy from food into ATP (adenosine triphosphate), which is the primary form of energy used by cells. They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of chemical energy. Mitochondria are also involved in various other cellular processes, such as signaling, differentiation, and apoptosis (programmed cell death).

Mitochondria have their own DNA, known as mitochondrial DNA (mtDNA), which is inherited maternally. This means that mtDNA is passed down from the mother to her offspring through the egg cells. Mitochondrial dysfunction has been linked to a variety of diseases and conditions, including neurodegenerative disorders, diabetes, and aging.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Temperature, in a medical context, is a measure of the degree of hotness or coldness of a body or environment. It is usually measured using a thermometer and reported in degrees Celsius (°C), degrees Fahrenheit (°F), or kelvin (K). In the human body, normal core temperature ranges from about 36.5-37.5°C (97.7-99.5°F) when measured rectally, and can vary slightly depending on factors such as time of day, physical activity, and menstrual cycle. Elevated body temperature is a common sign of infection or inflammation, while abnormally low body temperature can indicate hypothermia or other medical conditions.

"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Magnesium is an essential mineral that plays a crucial role in various biological processes in the human body. It is the fourth most abundant cation in the body and is involved in over 300 enzymatic reactions, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium also contributes to the structural development of bones and teeth.

In medical terms, magnesium deficiency can lead to several health issues, such as muscle cramps, weakness, heart arrhythmias, and seizures. On the other hand, excessive magnesium levels can cause symptoms like diarrhea, nausea, and muscle weakness. Magnesium supplements or magnesium-rich foods are often recommended to maintain optimal magnesium levels in the body.

Some common dietary sources of magnesium include leafy green vegetables, nuts, seeds, legumes, whole grains, and dairy products. Magnesium is also available in various forms as a dietary supplement, including magnesium oxide, magnesium citrate, magnesium chloride, and magnesium glycinate.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

Enzyme precursors are typically referred to as zymogens or proenzymes. These are inactive forms of enzymes that can be activated under specific conditions. When the need for the enzyme's function arises, the proenzyme is converted into its active form through a process called proteolysis, where it is cleaved by another enzyme. This mechanism helps control and regulate the activation of certain enzymes in the body, preventing unwanted or premature reactions. A well-known example of an enzyme precursor is trypsinogen, which is converted into its active form, trypsin, in the digestive system.

Peptides are short chains of amino acid residues linked by covalent bonds, known as peptide bonds. They are formed when two or more amino acids are joined together through a condensation reaction, which results in the elimination of a water molecule and the formation of an amide bond between the carboxyl group of one amino acid and the amino group of another.

Peptides can vary in length from two to about fifty amino acids, and they are often classified based on their size. For example, dipeptides contain two amino acids, tripeptides contain three, and so on. Oligopeptides typically contain up to ten amino acids, while polypeptides can contain dozens or even hundreds of amino acids.

Peptides play many important roles in the body, including serving as hormones, neurotransmitters, enzymes, and antibiotics. They are also used in medical research and therapeutic applications, such as drug delivery and tissue engineering.

A Structure-Activity Relationship (SAR) in the context of medicinal chemistry and pharmacology refers to the relationship between the chemical structure of a drug or molecule and its biological activity or effect on a target protein, cell, or organism. SAR studies aim to identify patterns and correlations between structural features of a compound and its ability to interact with a specific biological target, leading to a desired therapeutic response or undesired side effects.

By analyzing the SAR, researchers can optimize the chemical structure of lead compounds to enhance their potency, selectivity, safety, and pharmacokinetic properties, ultimately guiding the design and development of novel drugs with improved efficacy and reduced toxicity.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

SERPINs are an acronym for "serine protease inhibitors." They are a group of proteins that inhibit serine proteases, which are enzymes that cut other proteins. SERPINs are found in various tissues and body fluids, including blood, and play important roles in regulating biological processes such as inflammation, blood clotting, and cell death. They do this by forming covalent complexes with their target proteases, thereby preventing them from carrying out their proteolytic activities. Mutations in SERPIN genes have been associated with several genetic disorders, including emphysema, cirrhosis, and dementia.

A catalytic domain is a portion or region within a protein that contains the active site, where the chemical reactions necessary for the protein's function are carried out. This domain is responsible for the catalysis of biological reactions, hence the name "catalytic domain." The catalytic domain is often composed of specific amino acid residues that come together to form the active site, creating a unique three-dimensional structure that enables the protein to perform its specific function.

In enzymes, for example, the catalytic domain contains the residues that bind and convert substrates into products through chemical reactions. In receptors, the catalytic domain may be involved in signal transduction or other regulatory functions. Understanding the structure and function of catalytic domains is crucial to understanding the mechanisms of protein function and can provide valuable insights for drug design and therapeutic interventions.

A plasmid is a small, circular, double-stranded DNA molecule that is separate from the chromosomal DNA of a bacterium or other organism. Plasmids are typically not essential for the survival of the organism, but they can confer beneficial traits such as antibiotic resistance or the ability to degrade certain types of pollutants.

Plasmids are capable of replicating independently of the chromosomal DNA and can be transferred between bacteria through a process called conjugation. They often contain genes that provide resistance to antibiotics, heavy metals, and other environmental stressors. Plasmids have also been engineered for use in molecular biology as cloning vectors, allowing scientists to replicate and manipulate specific DNA sequences.

Plasmids are important tools in genetic engineering and biotechnology because they can be easily manipulated and transferred between organisms. They have been used to produce vaccines, diagnostic tests, and genetically modified organisms (GMOs) for various applications, including agriculture, medicine, and industry.

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which remains unchanged at the end of the reaction. A catalyst lowers the activation energy required for the reaction to occur, thereby allowing the reaction to proceed more quickly and efficiently. This can be particularly important in biological systems, where enzymes act as catalysts to speed up metabolic reactions that are essential for life.

Pancreatic elastase is a type of elastase that is specifically produced by the pancreas. It is an enzyme that helps in digesting proteins found in the food we eat. Pancreatic elastase breaks down elastin, a protein that provides elasticity to tissues and organs in the body.

In clinical practice, pancreatic elastase is often measured in stool samples as a diagnostic tool to assess exocrine pancreatic function. Low levels of pancreatic elastase in stool may indicate malabsorption or exocrine pancreatic insufficiency, which can be caused by various conditions such as chronic pancreatitis, cystic fibrosis, or pancreatic cancer.

Mitochondrial proton-translocating ATPases, also known as F1F0-ATP synthase or complex V, are enzyme complexes found in the inner mitochondrial membrane of eukaryotic cells. They play a crucial role in the process of oxidative phosphorylation, which generates ATP (adenosine triphosphate), the primary energy currency of the cell.

These enzyme complexes consist of two main parts: F1 and F0. The F1 portion is located on the matrix side of the inner mitochondrial membrane and contains the catalytic sites for ATP synthesis. It is composed of three α, three β, and one γ subunits, along with additional subunits that regulate its activity.

The F0 portion spans the inner mitochondrial membrane and functions as a proton channel. It is composed of multiple subunits, including a, b, and c subunits, which form a rotor-stator structure. As protons flow through this channel due to the electrochemical gradient established by the electron transport chain, the rotation of the F0 rotor drives the synthesis of ATP in the F1 portion.

Mitochondrial proton-translocating ATPases are highly conserved across different species and play a vital role in maintaining energy homeostasis within the cell. Dysfunction in these enzyme complexes can lead to various mitochondrial disorders and diseases, such as neurodegenerative disorders, muscle weakness, and metabolic abnormalities.

HeLa cells are a type of immortalized cell line used in scientific research. They are derived from a cancer that developed in the cervical tissue of Henrietta Lacks, an African-American woman, in 1951. After her death, cells taken from her tumor were found to be capable of continuous division and growth in a laboratory setting, making them an invaluable resource for medical research.

HeLa cells have been used in a wide range of scientific studies, including research on cancer, viruses, genetics, and drug development. They were the first human cell line to be successfully cloned and are able to grow rapidly in culture, doubling their population every 20-24 hours. This has made them an essential tool for many areas of biomedical research.

It is important to note that while HeLa cells have been instrumental in numerous scientific breakthroughs, the story of their origin raises ethical questions about informed consent and the use of human tissue in research.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

... (ClpP) is an enzyme that in humans is encoded by the CLPP gene. This protein is ... ATP-dependent protease from Escherichia coli". The Journal of Biological Chemistry. 262 (10): 4477-4485. doi:10.1016/S0021-9258 ... "Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP". The Journal of Biological ... Wang J, Hartling JA, Flanagan JM (November 1997). "The structure of ClpP at 2.3 A resolution suggests a model for ATP-dependent ...
... the ATP-dependent Clp protease adaptor protein ClpS is a bacterial protein. In the bacterial cytosol, ATP-dependent protein ... Endopeptidase Clp Clp protease family Varshavsky A (August 2011). "The N-end rule pathway and regulation by proteolysis". ... The protein substrate is then degraded by the ClpAP protease. In molecular biology, ... degradation is performed by several different chaperone-protease pairs, including ClpAP. ClpS directly influences the ClpAP ...
Partial substrate degradation by ATP-dependent proteases". IUBMB Life. 66 (5): 309-317. doi:10.1002/iub.1271. PMID 24823973. ... Later, the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered ... After a protein has been ubiquitinated, it is recognized by the 19S regulatory particle in an ATP-dependent binding step. The ... Ciehanover A, Hod Y, Hershko A (April 1978). "A heat-stable polypeptide component of an ATP-dependent proteolytic system from ...
Lon proteases are ATP-dependent serine peptidases belonging to the MEROPS peptidase family S16 (Lon protease family, clan SJ). ... "A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease". Proc. Natl. Acad. Sci. U.S.A ... Van Dyck L, Pearce DA, Sherman F (January 1994). "PIM1 encodes a mitochondrial ATP-dependent protease that is required for ... "Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules". ...
Lon protease is a member of ATP-dependent proteases (AAA+ proteases). Mature LONP1 is catalytically active in its homohexameric ... "A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease". Proceedings of the National ... Lu B, Liu T, Crosby JA, Thomas-Wohlever J, Lee I, Suzuki CK (March 2003). "The ATP-dependent Lon protease of Mus musculus is a ... Lu B, Liu T, Crosby JA, Thomas-Wohlever J, Lee I, Suzuki CK (March 2003). "The ATP-dependent Lon protease of Mus musculus is a ...
Van Dyck L, Langer T (November 1999). "ATP-dependent proteases controlling mitochondrial function in the yeast Saccharomyces ... ATP-dependent metalloprotease YME1L1 is an enzyme that in humans is encoded by the YME1L1 gene. YME1L1 belongs to the AAA ... an ATP/GTP binding motif, and a HEXXH motif typical of a zinc-dependent binding domain. YME1L1 is embedded in the inner ... Anand R, Wai T, Baker MJ, Kladt N, Schauss AC, Rugarli E, Langer T (March 2014). "The i-AAA protease YME1L and OMA1 cleave OPA1 ...
... (EC, endopeptidase Ti, caseinolytic protease, protease Ti, ATP-dependent Clp protease, ClpP, Clp ... Endopeptidase CLP protease family ATP-dependent Clp protease proteolytic subunit Gottesman S, Clark WP, Maurizi MR (May 1990 ... Maurizi MR, Thompson MW, Singh SK, Kim SH (1994). Endopeptidase Clp: ATP-dependent Clp protease from Escherichia coli. Methods ... "The ATP-dependent Clp protease of Escherichia coli. Sequence of clpA and identification of a Clp-specific substrate". The ...
The ATP-dependent proteases are shown to maintain the level of regulatory proteins and to get rid of any misfolded or damaged ... Along with the ATP-dependent proteases, the small RNA molecules are an important part of this response. For example, one of ... Susan Gottesman is known for her work with small RNAs and ATP-dependent proteases. Her work in these subjects has been ... In Gottesman's studies, she showed that the ATP-dependent proteases are regulated by the delivery of their substrate molecules ...
Endopeptidase Clp ATP-dependent Clp protease proteolytic subunit Maurizi MR, Clark WP, Katayama Y, Rudikoff S, Pumphrey J, ... ClpP is an ATP-dependent protease that cleaves a number of proteins, such as casein and albumin. It exists as a heterodimer of ... the proteolytic component of the ATP-dependent Clp protease of Escherichia coli". The Journal of Biological Chemistry. 265 (21 ... encoding a mitochondrial ATP-dependent chambered protease". American Journal of Human Genetics. 92 (4): 605-13. doi:10.1016/j. ...
ATP-dependent serine proteinase, lon proteinase, protease La, proteinase La, ATP-dependent lon proteinase, ATP-dependent ... A heat-shock gene which encodes the ATP-dependent protease La". The Journal of Biological Chemistry. 263 (24): 11718-28. doi: ... Larimore FS, Waxman L, Goldberg AL (April 1982). "Studies of the ATP-dependent proteolytic enzyme, protease La, from ... gene lon protease, gene lon proteins, PIM1 protease, PIM1 proteinase, serine protease La) is an enzyme. This enzyme catalyses ...
Only two ATP-dependent proteases are found in archaea: the membrane associated LonB protease and a soluble 20S proteosome ... Some proteases are less active after autolysis (e.g. TEV protease) whilst others are more active (e.g. trypsinogen). Proteases ... The activity of proteases is inhibited by protease inhibitors. One example of protease inhibitors is the serpin superfamily. It ... Proteases can be classified into seven broad groups: Serine proteases - using a serine alcohol Cysteine proteases - using a ...
ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial is an enzyme that in humans is encoded by the CLPX gene ... we can distinctly see its similarities and differences in the Clp protease. Bacteria use the ATP-dependent ClpX protease for a ... The complex assembly of the regulatory subunits of ATP-dependent Clp proteases is induced in the critical role in cellular ... an alternative subunit for the ATP-dependent Clp protease of Escherichia coli. Sequence and in vivo activities". The Journal of ...
The polyubiquinated protein is targeted to an ATP-dependent protease complex, the proteasome. The ubiquitin is released and ... Cysteine protease Serine protease Threonine protease Aspartic protease Glutamic protease Metalloprotease Asparagine peptide ... Proteases may be regulated by antiproteases or protease inhibitors, and imbalance between proteases and antiproteases can ... The proteases used have high degree of specificity, such as thrombin, enterokinase, and TEV protease, so that only the targeted ...
The protein encoded by this gene is an ATP-dependent protease that likely plays a role in maintaining overall peroxisome ... "Cleavage site selection within a folded substrate by the ATP-dependent lon protease". J. Biol. Chem. 280 (26): 25103-10. doi: ...
It uses the helicase ATP hydrolysis site to remove the γ-phosphate from the 5′ end of the RNA. The N-terminal domain of the non ... One of the products cleaved is a RNA-dependent RNA polymerase, responsible for the synthesis of a negative-sense RNA molecule. ... Once translated, the polyprotein is cleaved by a combination of viral and host proteases to release mature polypeptide products ... RNA binding affinity is reduced by the presence of ATP or GTP and enhanced by S-adenosyl methionine. This protein also encodes ...
Encoding a Mitochondrial ATP-Dependent Chambered Protease". The American Journal of Human Genetics. 92 (4): 605-613. doi: ... a mitochondrial protease RMND1, a protein involved in mitochondrial translation; causes kidney problems on top of classical ...
The RadA/Sms family are probable ATP-dependent proteases involved in both DNA repair and degradation of proteins, peptides, ... It binds ATP. Due to the lack of a nucleus in these organisms, there was doubt as to whether or not cyanobacteria would be able ... They did this by adding KaiA, KaiB, KaiC, and ATP into a test tube in the approximate ratio recorded in vivo. They then ... In both systems the circadian period is dependent on the interactions between proteins within the cell, and when the genes for ...
Clp-family proteins are ATP-dependent proteases which play a crucial role in the cell function by degrading misfolded proteins ... activation of casein lytic protease (ClpP) which is an important bacterial protease. Most antibiotics work through inhibitory ... They bind to ClpP and allow the protease to degrade proteins without the help of an ATPase. ADEP4/ClpP complexes target ... This process is tightly regulated with the hydrolysis of ATP to prevent uncontrolled protein or peptide degradation that would ...
PreP is an Zn2+-dependent and ATP-independent metalloprotease, it doesn't select substrates on the basis of post-translational ... Sauer RT, Baker TA (2011). "AAA+ proteases: ATP-fueled machines of protein destruction". Annual Review of Biochemistry. 80: 587 ... PreP is the Aβ-degrading protease in mitochondria. Immune-depletion of PreP in brain mitochondria prevents degradation of ... Chen J, Teixeira PF, Glaser E, Levine RL (December 2014). "Mechanism of oxidative inactivation of human presequence protease by ...
Higgins JJ, Pucilowska J, Lombardi RQ, Rooney JP (November 2004). "A mutation in a novel ATP-dependent Lon protease gene in a ...
Kanemori M, Nishihara K, Yanagi H, Yura T (December 1997). "Synergistic roles of HslVU and other ATP-dependent proteases in ... 1996). HslV-HslU: A novel ATP-dependent protease complex in Escherichia coli related to the eukaryotic proteasome. Proc Natl ... by the ATP-dependent HslVU protease from Escherichia coli". FEBS Letters. 553 (3): 351-4. doi:10.1016/s0014-5793(03)01044-5. ... "Purification and characterization of the heat shock proteins HslV and HslU that form a new ATP-dependent protease in ...
... the ATP-dependent substrate specificity component of the ClpP-ClpX protease, is a novel molecular chaperone". The EMBO Journal ... Blond-Elguindi S, Fourie AM, Sambrook JF, Gething MJ (June 1993). "Peptide-dependent stimulation of the ATPase activity of the ... Non-chaperonin molecular chaperone ATPase (EC, molecular chaperone Hsc70 ATPase) is an enzyme with systematic name ATP ... "Unfolded proteins stimulate molecular chaperone Hsc70 ATPase by accelerating ADP/ATP exchange". Biochemistry. 31 (39): 9406-12 ...
The predicted structure is Chain A, crystal structure analysis of Clpb, a protein that encodes an ATP-dependent protease and ...
This rapid synthesis indicates that there is an ATP-dependent interaction where the formed HSP60 complex stabilizes the ... The subsequent protease-resistant HSP60 is formed in a half-time of 5-10 minutes. ... The addition of ATP and GroES has a drastic effect on the conformation of the cis domain. This effect is caused by flexion and ... Hydrolysis of ATP and binding of a new substrate protein to the opposite cavity sends an allosteric signal causing GroES and ...
The product of the lon (capR) gene in Escherichia coli is the ATP-dependent protease, protease La. Proc Natl Acad Sci U S A. ... Escherichia coli contains a soluble ATP-dependent protease (Ti) distinct from protease La. Proc Natl Acad Sci U S A. 1987 Aug; ... gene in Escherichia coli is the ATP-dependent protease, protease la". Proceedings of the National Academy of Sciences of the ... "Escherichia coli contains a soluble ATP-dependent protease (Ti) distinct from protease la". Proceedings of the National Academy ...
This large family of proteins mediate docking of synaptic vesicles in an ATP-dependent manner. With the help of synaptobrevin ... The botulinum toxin has protease activity which degrades the SNAP-25 protein. The SNAP-25 protein is required for vesicle ... The ability of SNAREs to mediate fusion in a calcium-dependent manner recently has been reconstituted in vitro. Consistent with ... The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between ...
... and which can activate harmful calcium-dependent proteases such as calpain. Reactive oxygen species (ROS) are also produced as ... ATP. This produces an energy deficit in the cell, just when it most needs ATP to fuel activity of ion pumps. MPT also allows ... opening of the mitochondrial permeability transition pore can greatly reduce ATP production, and can cause ATP synthase to ... "Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death". Nature Cell Biology. 9 (5): 550-555. ...
Similarly, because host Hfl-proteases degrade proteins in an ATP dependent manner, coupling cII levels to Hfl-protease activity ... Host protease dependent degradation: C-terminal degradation tag is recognized by host HflA and HflB proteases, quickly ... This tag is recognized by host proteases HflA and HflB, cause rapid proteolysis cII. Although the C-terminal tag is still ... Krinke L, Wulff DL (December 1990). "RNase III-dependent hydrolysis of lambda cII-O gene mRNA mediated by lambda OOP antisense ...
ClpS is as a specific adaptor protein for the ATP-dependent AAA+ protease ClpAP, and hence ClpS delivers N-degron substrates to ... it involves the Clp protease system which consists of the adaptor protein ClpS and the ClpA/P chaperone and protease core. A ... June 2013). "ClpS1 is a conserved substrate selector for the chloroplast Clp protease system in Arabidopsis". The Plant Cell. ... Nishimura K, van Wijk KJ (September 2015). "Organization, function and substrates of the essential Clp protease system in ...
... triggering the ATP-dependent unfolding of the target protein that allows passage into the proteasome's 20S core particle, where ... proteases degrade the target into short peptide fragments for recycling by the cell. A ubiquitin-activating enzyme, or E1, ...
ATP-dependent Clp protease proteolytic subunit (ClpP) is an enzyme that in humans is encoded by the CLPP gene. This protein is ... ATP-dependent protease from Escherichia coli". The Journal of Biological Chemistry. 262 (10): 4477-4485. doi:10.1016/S0021-9258 ... "Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP". The Journal of Biological ... Wang J, Hartling JA, Flanagan JM (November 1997). "The structure of ClpP at 2.3 A resolution suggests a model for ATP-dependent ...
Protein target information for ATP-dependent Clp protease proteolytic subunit (Laribacter hongkongensis HLHK9). Find diseases ...
Indeed, ATP dependent and independent proteases are identified to be very critical in balancing anterograde to retrograde ... An Overview on ATP Dependent and Independent Proteases Including an Anterograde to Retrograde Control on Mitochondrial Function ... Diabetes, mitochondrial dysfunction, ATP dependent and independent proteases, mitochondrial genome, anterograde pathways, ... However, the regulation of these proteases at gene level is not clearly understood and still research is warranted. In this ...
MexAM1_META2p0891 6830944 putative ATP-dependent protease ATP-binding subunit (RefSeq). × Error message. *Unable to create ... O) COG542 , ATPases with chaperone activity, ATP-binding subunit Protein fate, Protein folding and stabilization ...
Evidence that two ATP-dependent (Lon) proteases in Borrelia burgdorferi serve different functions. PLoS pathogens. 2009 Nov;5( ... Evidence that two ATP-dependent (Lon) proteases in Borrelia burgdorferi serve different functions. In: PLoS pathogens. 2009 ; ... Evidence that two ATP-dependent (Lon) proteases in Borrelia burgdorferi serve different functions. / Coleman, James L.; Katona ... N2 - The canonical ATP-dependent protease Lon participates in an assortment of biological processes in bacteria, including the ...
ATP-Dependent Clp Protease Subunit C1, HvClpC1, Is a Strong Candidate Gene for Barley Variegation Mutant luteostrians as ... Mingjiu Li, Ganggang Guo, Hélène Pidon, Michael Melzer, Alberto R. Prina, et al.. ATP-Dependent Clp Protease Subunit C1, ...
ClpS; ATP-dependent Clp protease adaptor protein ClpS. RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10 The following ... involved_in ubiquitin-dependent protein catabolic process via the N-end rule pathway IBA Inferred from Biological aspect of ... Ubc2/Rad6 ser(120) regulates ubiquitin-dependent N-end rule targeting by E3{alpha}/Ubr1 Title: Ser(120) of Ubc2/Rad6 regulates ... identification of whole exon deletions and duplications in the UBR1 gene by multiplex ligation-dependent probe amplification ...
ATP-dependent protease ATP-binding subunit. No expression. +. −. Burkholderia pseudomallei. YP_334398.2. Full length. Adenosine ... FAD-dependent thymidylate synthase. ND. +. ++. Ehrlichia ruminantium. YP_196632.1. Bp 96-762. FAD-dependent thymidylate ... FAD-dependent thymidylate synthase. ND. ++. +. Leishmania infantum. XP_001464664.1. Full length. Elongation factor 1α. ... ABC transporter/ATP-binding protein. Insoluble. ++. ++. Bartonella henselae. YP_034187.1. Full length. Holliday junction DNA ...
ATP-dependent Clp protease ATP-binding subunit ClpL (ClpL). Q7A3F4. 1.53 ↑. 14. Fructose-bisphosphate aldolase class 1 (Fda). ... ATP-dependent 6-phosphofructokinase (PfkA). P99165. 1.55 ↓. 9. 2,3-bisphosphoglycerate-independent phosphoglycerate mutase ( ... ATP-Dependent Ligases and AEP Primases Affect the Profile and Frequency of Mutations in Mycobacteria under Oxidative Stress ... and cysteine protease, staphopain B (SspB)), and cell membrane-bounded ATP synthase subunit α (AtpA), all the other ...
ATP-dependent Lon protease PIM1 Feature Type. ORF , Verified EC Number. ...
Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. Am J Hum ...
PDB Compounds: (E:) ATP-dependent CLP protease, putative. SCOPe Domain Sequences for d2f6ie3:. Sequence; same for both SEQRES ... PDB Description: Crystal structure of the ClpP protease catalytic domain from Plasmodium falciparum ...
The crystal structure of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli at 1.5 A resolution.. Krzywda, S ... Crystallization of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli. Krzywda, S., Brzozowski, A.M.,& ... Eubacteria and eukaryotic cellular organelles have membrane-bound ATP-dependent proteases, which degrade misassembled membrane ... Eubacteria and eukaryotic cellular organelles have membrane-bound ATP-dependent proteases, which degrade misassembled membrane ...
PDB Compounds: (B:) ATP-dependent clp protease proteolytic subunit 1. SCOPe Domain Sequences for d2cbyb_:. Sequence, based on ... PDB Description: crystal structure of the atp-dependent clp protease proteolytic subunit 1 (clpp1) from mycobacterium ...
Two mitochondrial proteases that regulate proteostasis in the matrix are the ATP-dependent Clp protease (ClpP) and Lon protease ... ATP-dependent Clp protease (ClpP), a mitochondrial matrix protease, plays an important role in regulating mitochondrial protein ... Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP. J Biol Chem 277:21095-21102. https ... 1b). In contrast, expression of either αSyn WT or A53T had no effect on the mitochondrial matrix protease LonP or the ClpP ATP- ...
ATP-dependent protease HslVU, ATPase subunit. 100. 410. 2.10E−229. Campylobacter spp.. Multispecies GTP-binding protein. 100. ...
Acidosis, therefore, stimulates selectively an ATP-dependent, nonlysosomal, proteolytic process. We also examined whether the ... Eosinophils are prominent in bullous pemphigoid (BP), and proteases secreted from these and other inflammatory cells may induce ... but do not prove that acidosis stimulates muscle proteolysis by activating the ATP-ubiquitin-proteasome-dependent, proteolytic ... However, when ATP production was also blocked, proteolysis fell to the same low level in muscles of acidotic and control rats. ...
PolyP forms a complex with the ATP-dependent Lon protease. The formation of a complex then enables Lon to degrade free ... Each protease was purified to homogeneity and characterized. The purified expro-I was a non-alkaline serine protease with an ... Oyster extract was prepared by hydrolysis of oyster protein with proteases, Aloase (a protease from Bacillus subtilis), and ... It was activated by Fe2+, which has never been reported as a bacterial protease activator. At a concentration of 7.5% (w/v) ...
Recombinant Mycoplasma pneumoniae Lon protease (lon), partial , CSB-EP305230MLW , CusabioAlternative Name(s): ATP-dependent ... Recombinant Mycoplasma pneumoniae Lon protease (lon), partial , CSB-EP305230MLW Cusabio Mycoplasma pneumoniae Recombinants ...
An interconnected highly integrated system of mitochondrial and cytosolic chaperones and proteases along with the fission/ ... the ATP-dependent proteases, namely, the LON protease and the Clp Protease Proteolytic subunit (CLPP) and the mitochondrial AAA ... S. H. Bernstein, S. Venkatesh, M. Li et al., "The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death ... L. Waxman and A. L. Goldberg, "Protease La, the lon gene product, cleaves specific fluorogenic peptides in an ATP-dependent ...
ATP-dependent protease La (LON) domain protein (AT2G25740) Antibodies. cereblon (Crbn) Antibodies. 2610203G15Rik Antibodies. ... This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found ... An, Ponthier, Sack, Seebacher, Stadler, Donovan, Fischer: "pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate ... "Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations." in: Nature ...
ATP-dependent serine proteinase; lon proteinase; protease La; proteinase La; ATP-dependent lon proteinase; ATP-dependent ... A heat-shock gene which encodes the ATP-dependent protease La. J. Biol. Chem. 263 (1988) 11718-11728. [PMID: 3042779] ... Larimore, F.S., Waxman, L. and Goldberg, A.L. Studies of the ATP-dependent proteolytic enzyme, protease La, from Escherichia ... gene lon protease; gene lon proteins; PIM1 protease; PIM1 proteinase; serine protease La. ...
It is part of the m-AAA protease, an adenosine triphosphate (ATP) ̶ dependent proteolytic complex located at the mitochondrial ... Penetrance is age dependent and high. Other genes involved in autosomal dominant HSPs are SPG8, SPG10, SPG13, SPG31, and SPG33. ... Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. The m-AAA protease defective in hereditary spastic paraplegia ...
2000The YELLOW VARIEGATED (VAR2) locus encodes a homologue of FtsH, an ATP-dependent protease in ArabidopsisPlant Cell Physiol ... The oxidized ATP synthase might be degraded by mitochondrial FtsH homologs, m-AAA and i-AAA proteases, which have an essential ... 2018FtsH protease in the thylakoid membrane: Physiological functions and the regulation of protease activityFront Plant Sci. 9: ... a membrane-bound ATP-dependent zinc metalloprotease that degrades membrane proteins in a processive manner, although several ...
... unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and ... We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations ... Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, ... Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP- ...
Eytan E, Ganoth D, Armon T, Hershko A. ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins ... Tokunaga F, Goto T, Koide T, et al ATP- and antizyme-dependent endoproteolysis of ornithine decarboxylase to oligopeptides by ... 50-80% dose-dependent decrease in tumor volume Murine lung cancer and human breast cancer (92) Lewis lung model, EMT-6 mouse ... 50-80% dose-dependent decrease in tumor volume Murine lung cancer and human breast cancer (92) Lewis lung model, EMT-6 mouse ...
E3 ligase-dependent SUMOylation). However, SUMO-specific proteases could remove the SUMO protein from the substrate. STUbls ... Then, mature SUMO is directly activated by SUMO E1 via ATP hydrolysis. Upon interaction of the charged E1 enzyme with E2, SUMO ... and ubiquitin-specific protease-like 1(USPL1) (57, 58). Compared to the SENP protease, the three novel SUMO-specific proteases ... With the discovery of sentrin-specific protease 1 (SENP1) (55), more SUMO-specific proteases have been discovered, including ...
ATP-Dependent Proteases Entry term(s). ATP Dependent Protease ATP Dependent Proteases ATP Requiring Protease ATP-Dependent ... ATP-dependent proteases Entry term(s):. ATP Dependent Protease. ATP Dependent Proteases. ATP Requiring Protease. ATP-Dependent ... Adenosine Triphosphate-Dependent Proteolytic System Protease, ATP-Dependent Protease, ATP-Requiring Proteases, ATP-Dependent ... Adenosine Triphosphate-Dependent Proteolytic System. Protease, ATP-Dependent. Protease, ATP-Requiring. Proteases, ATP-Dependent ...
  • ATP-dependent Clp protease proteolytic subunit (ClpP) is an enzyme that in humans is encoded by the CLPP gene. (
  • The work supports a role for chemical modification in the recognition and subsequent degradation of a key protein subunit of PSII by a bacterial-type protease, suggesting that tryptophan oxidation of components of the photosynthetic apparatus after high light stress plays a critical role in initiating the PSII repair system. (
  • Enzyme ClpP is a highly conserved serine protease present throughout bacteria and also found in the mitochondria and chloroplasts of eukaryotic cells. (
  • A fully assembled Clp protease complex has a barrel-shaped structure in which two stacked ring of proteolytic subunits (ClpP or ClpQ) are either sandwiched between two rings or single-caped by one ring of ATPase-active chaperon subunits (ClpA, ClpC, ClpE, ClpX or ClpY). (
  • P. aeruginosa produces two forms of the ClpP peptidase, PaClpP114 and PaClpP17P27, which in complex with ClpX or ClpA form functional proteases. (
  • ClpP protease is a major contributor for mitochondrial protein quality control system and removing damaged or misfolded proteins in mitochondrial matrix. (
  • Defects in mitochondrial Clp proteases have been associated with the progression of neurodegenerative diseases while upregulation of ClpP proteases has been implicated in preventing premature aging. (
  • On the chromosome, lon-2 is immediately downstream of ATP-dependent proteases clpP and clpX, an arrangement identical to that of lon of Escherichia coli. (
  • Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. (
  • ATP-dependent Clp protease (ClpP), a mitochondrial matrix protease, plays an important role in regulating mitochondrial protein turnover and bioenergetics activity. (
  • We have determined a 2.1 Angstrom crystal structure for human mitochondrial ClpP (hClpP), the proteolytic component of the ATP-dependent ClpXP protease. (
  • In several bacteria, such as E. coli, proteins tagged with the SsrA peptide (ANDENYALAA) encoded by tmRNA are digested by Clp proteases. (
  • Proteases target damaged or misfolded proteins, transcription factors and signaling proteins in bacteria to coordinate complex cell responses and thus they have robust importance for the physiology and virulence of bacteria. (
  • The protein encoded by this gene belongs to the peptidase family S14 and hydrolyzes proteins into small peptides in the presence of ATP and magnesium. (
  • The canonical ATP-dependent protease Lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. (
  • The 26S proteasome is the principal ATP-dependent protease in eukaryotic cells and responsible for the majority of targeted protein turnover, both through the degradation of short-lived regulatory proteins and the clearance of damaged or misfolded polypeptides for protein-quality control ( Hershko and Ciechanover, 1998 ). (
  • ClpXP is a two-component ATP-dependent protease that unfolds and degrades proteins bearing specific recognition signals. (
  • These included secreted proteins, an LPS glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin biosynthesis, and Clp protease adaptor (CIpS). (
  • These included ATP-dependent Clp protease, CIpS, and proteins of unknown function. (
  • Proteases determine the lifetime of other proteins playing an important physiological role like hormones, antibodies, or other enzymes-this is one of the fastest "switching on" and "switching off" regulatory mechanisms in the physiology of an organism. (
  • Bacteria also secrete proteases to hydrolyze (digest) the peptide bonds in proteins and therefore break the proteins down into their constituent monomers (amino acids). (
  • Bacterial and fungal proteases are particularly important to the global carbon and nitrogen cycles in the recycling of proteins, and such activity tends to be regulated by nutritional signals in these organisms. (
  • The net impact of nutritional regulation of protease activity among the thousands of species present in soil can be observed at the overall microbial community level as proteins are broken down in response to carbon, nitrogen, or sulfur limitation. (
  • This tags IκB for poly-ubiquitination and subsequent degradation through the 26S proteasome [ 5 ], a multi-catalytic, ATP-dependent protease complex, responsible for posttranslational control of all short-lived and many long-lived proteins. (
  • Acid proteases secreted into the stomach (such as pepsin) and serine proteases present in duodenum (trypsin and chymotrypsin) enable us to digest the protein in food. (
  • Borrelia spirochetes are unusual in that they code for two putative ATP-dependent Lon homologs, Lon-1 and Lon-2. (
  • To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. (
  • In photosynthetic organisms, maintenance of photosynthetic light reaction is manifested by so called Photosystem II (PSII) repair system, where the reaction center protein D1 is targeted to photo-oxidative damage and rapidly degraded by the processive protease FtsH. (
  • Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. (
  • This protein is an essential component to form the protein complex of Clp protease (Endopeptidase Clp). (
  • Different experimental studies conducted on silencing the genes of these proteases have shown embryonic lethality, cancer cells death, increased hepatic glucose output, insulin tolerance, increased protein exclusion bodies, mitochondrial dysfunction, and defect in mitochondrial biogenesis, increased inflammation, Apoptosis etc. (
  • Eubacteria and eukaryotic cellular organelles have membrane-bound ATP-dependent proteases, which degrade misassembled membrane protein complexes and play a vital role in membrane quality control. (
  • Here I propose to call the polyP-Lon complex the "stringent protease," and I discuss new insights of protein degradation control in bacteria. (
  • This gene encodes a protein related to the Lon protease protein family. (
  • As in other protein unfoldases of the AAA+ family, the six Rpt subunits in the proteasome base use loops with conserved aromatic residues projecting into the central pore of the hexamer to interact with the substrate polypeptide, mechanically pull on it, and drive its translocation into the 20S core in an ATP hydrolysis-dependent manner. (
  • A protease is an enzyme that conducts proteolysis, i.e., the protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain which form the protein. (
  • Proteases are involved in digesting long protein chains into short fragments, splitting the peptide bonds that link amino acid residues. (
  • Proteases can either break specific peptide bonds, depending on the amino acid sequence of a protein, or break down a complete peptide to amino acids. (
  • Amplite™ Universal Fluorimetric Protease Activity Assay Kit is an ideal choice to perform routine protease isolation assays or for identifying the presence of contaminating proteases in protein samples. (
  • It is part of the m-AAA protease, an adenosine triphosphate (ATP) ̶ dependent proteolytic complex located at the mitochondrial inner membrane, which controls protein quality and regulates ribosome assembly. (
  • A secreted bacterial protease may also act as an exotoxin, and be an example of a virulence factor in bacterial pathogenesis. (
  • Mitochondria are the energy producing organelles in eukaryotic cell providing ATP through oxidative phosphorylation (OXPHOS). (
  • Proteases that contain proteolytic core domains and ATPase-containing regulatory domains. (
  • Studies with bortezomib (VELCADE, formerly known as PS-341) and other proteasome inhibitors indicate that cancer cells are especially dependent on the proteasome for survival, and several mechanisms used by prostate cancer cells require proteasome function. (
  • The 26S proteasome is essential for proteostasis and the regulation of vital processes through ATP-dependent degradation of ubiquitinated substrates. (
  • The assay utilizes a fluorescent casein conjugate that is proven to be a generic substrate for a broad spectrum of proteases (e.g. trypsin, chymotrypsin, thermolysin, proteinase K, protease XIV, and elastase). (
  • Fully functional Clp protease requires the participation of AAA+ ATPase. (
  • Degradation of IκB frees NF-κB for translocation into the nucleus, where it binds to specific consensus sequences in promoter regions of NF-κB-dependent genes to initiate transcription of pro-inflammatory cytokines [ 6 ]. (
  • Intracellular proteases have a role in bacterial virulence. (
  • Here, we report that both pathways can be dissected by depletion of intracellular ATP. (
  • In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. (
  • Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. (
  • In this review, we articulated the origin and regulation of these proteases and the cross talk between the nucleus and mitochondria vice versa, and highlighted the role of these proteases in diabetes and diabetic complications in human diseases. (
  • Desautels, M. and Goldberg, A.L. Demonstration of an ATP-dependent, vanadate-sensitive endoprotease in the matrix of rat liver mitochondria. (
  • The other pathway is controlled by the release of cytochrome c from mitochondria and the subsequent ATP-dependent activation of the death regulator apoptotic protease-activating factor 1 (Apaf-1). (
  • Protease-catalyzed hydrolysis relieves its quenching effect, yielding brightly fluorescent dye-labeled short peptides. (
  • However, the regulation of these proteases at gene level is not clearly understood and still research is warranted. (
  • Because blood induction of Lon-1 may be of importance in the regulation of virulence factors critical for spirochete transmission, the clarification of functional roles for these two proteases in B. burgdorferi was the object of this study. (
  • The addition of microglia or ATP led to the disruption of the MBEC monolayer and significantly decreased barrier function as measured by trans-endothelial electrical resistance (TEER) and electric cell-substrate impedance sensing (ECIS). (
  • Expanding the mutational spectrum in Johanson-Blizzard syndrome: identification of whole exon deletions and duplications in the UBR1 gene by multiplex ligation-dependent probe amplification analysis. (
  • Protease assays are widely used for the investigation of protease inhibitors and the detection of protease activities. (
  • Other proteases are present in leukocytes (elastase and cathepsin G) and play several different roles in metabolic control. (
  • Proteases are used throughout an organism for various metabolic processes. (
  • Attachment of a protease to a certain group depends on the structure of catalytic site and the amino acid (as one of the constituents) essential for its activity. (
  • Monitoring various protease activities has become a routine task for many biological laboratories. (
  • The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate. (
  • Recombinant Lon-1 manifested properties of an ATP-dependent chaperone-protease in vitro but did not complement an E. coli Lon mutant, while Lon-2 corrected two characteristic Lon-mutant phenotypes. (
  • PolyP forms a complex with the ATP-dependent Lon protease. (
  • By complex cooperative action the proteases may proceed as cascade reactions, which result in rapid and efficient amplification of an organism's response to a physiological signal. (
  • NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. (
  • Both free EF (EF) and PA-bound-EF (ETx) have adenylyl cyclase activity converting ATP to cAMP. (
  • The three-step method includes magnetic immunocapture with monoclonal antibodies, reaction with ATP generating cAMP, and quantification of cAMP by isotope-dilution HPLC-MS/MS. Total EF was quantified from 5PL regression of cAMP vs ETx concentration. (
  • In conclusion, we offer evidence that microglia migration across the brain endothelial cell monolayer is increased in the presence of ATP in a manner that involves MMP secretion. (
  • The three toxemic phases were aligned with the three clinical stages of anthrax for fast and slow progression which showed that anthrax progression is toxin- rather than time-dependent. (
  • Proteases present in blood serum (thrombin, plasmin, Hageman factor, etc.) play an important role in blood-clotting, as well as blood clot lysis, and the correct action of the immune system. (
  • An interconnected highly integrated system of mitochondrial and cytosolic chaperones and proteases along with the fission/fusion machinery represents the surveillance scaffold of mitostasis. (
  • Currently there are no approved antimicrobial agents that target bacterial proteases. (