The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
An ATP-dependent enzyme that catalyzes the addition of ADP to alpha-D-glucose 1-phosphate to form ADP-glucose and diphosphate. The reaction is the rate-limiting reaction in prokaryotic GLYCOGEN and plant STARCH biosynthesis.
The rate dynamics in chemical or physical systems.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
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.
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 region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Ribonucleotide Reductases are enzymes that catalyze the conversion of ribonucleotides to deoxyribonucleotides, which is a crucial step in DNA synthesis and repair, utilizing a radical mechanism for this conversion.
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.
Glyceric acids are compounds that contain a glycerol moiety with one or more carboxylic acid groups, which can exist in various forms such as glycerate, glycerophosphate, and glyceronitrate, playing crucial roles in metabolism and energy production.
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.
Halogenated anti-infective agent that is used against trematode and cestode infestations.
An enzyme that catalyzes the conversion of carbamoyl phosphate and L-aspartate to yield orthophosphate and N-carbamoyl-L-aspartate. (From Enzyme Nomenclature, 1992) EC 2.1.3.2.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
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 assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
An isomerase that catalyzes the conversion of chorismic acid to prephenic acid. EC 5.4.99.5.
Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.
An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2.
An enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol. Dihydroxyacetone and L-glyceraldehyde can also act as acceptors; UTP and, in the case of the yeast enzyme, ITP and GTP can act as donors. It provides a way for glycerol derived from fats or glycerides to enter the glycolytic pathway. EC 2.7.1.30.
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.
5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
An allosteric enzyme that regulates glycolysis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-1,6-bisphosphate. D-tagatose- 6-phosphate and sedoheptulose-7-phosphate also are acceptors. UTP, CTP, and ITP also are donors. In human phosphofructokinase-1, three types of subunits have been identified. They are PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE; PHOSPHOFRUCTOKINASE-1, LIVER TYPE; and PHOSPHOFRUCTOKINASE-1, TYPE C; found in platelets, brain, and other tissues.
A computer simulation developed to study the motion of molecules over a period of time.
Amino acids containing an aromatic side chain.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
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.
An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.
An enzyme that catalyzes the oxidation of 3-phosphoglycerate to 3-phosphohydroxypyruvate. It takes part in the L-SERINE biosynthesis pathway.
The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The characteristic three-dimensional shape of a molecule.
Proteins prepared by recombinant DNA technology.
A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
Proteins obtained from ESCHERICHIA COLI.
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)
Proteins found in any species of bacterium.
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.
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.
The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
The bacterial sugar phosphotransferase system (PTS) that catalyzes the transfer of the phosphoryl group from phosphoenolpyruvate to its sugar substrates (the PTS sugars) concomitant with the translocation of these sugars across the bacterial membrane. The phosphorylation of a given sugar requires four proteins, two general proteins, Enzyme I and HPr and a pair of sugar-specific proteins designated as the Enzyme II complex. The PTS has also been implicated in the induction of synthesis of some catabolic enzyme systems required for the utilization of sugars that are not substrates of the PTS as well as the regulation of the activity of ADENYLYL CYCLASES. EC 2.7.1.-.
Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.
The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Glycogen is a multibranched polysaccharide of glucose serving as the primary form of energy storage in animals, fungi, and bacteria, stored mainly in liver and muscle tissues. (Two sentences combined as per your request)
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
An essential amino acid that is required for the production of HISTAMINE.
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11.
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.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
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.
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 sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Measurement of the intensity and quality of fluorescence.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.
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 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.

Allosteric regulation of even-skipped repression activity by phosphorylation. (1/3161)

The Drosophila homeodomain protein Even-skipped (Eve) is a well characterized transcriptional repressor. Here, we show that Eve's ability to function in vitro is negatively regulated by phosphorylation. DNA-binding activity was unaffected by phosphorylation, but phosphorylated Eve was unable to interact with the TATA-binding protein (TBP), a known target for repression. Unexpectedly, phosphorylation of the Eve N terminus, which is dispensable for repression and TBP binding, was necessary and sufficient to inactivate Eve. LiCl, which specifically inhibits glycogen synthase kinase-3 (GSK-3), reduced Eve phosphorylation in nuclear extract and blocked inhibition of repression. In addition, Eve was phosphorylated and inactivated by purified GSK-3 beta plus casein kinase II. Our results suggest a novel mechanism of transcriptional control involving phosphorylation-induced allosteric interference with a repressive protein-protein interaction.  (+info)

Regulation of AMP deaminase from chicken erythrocytes. A kinetic study of the allosteric interactions. (2/3161)

The allosteric properties of AMP deaminase [EC 3.5.4.6] from chicken erythrocytes have been qualitatively and quantitatively accounted for by the concerted transition theory of Monod et al., on the assumption that this enzyme has different numbers of binding sites for each ligand. Theoretical curves yield a satisfactory fit for all experimental saturation functions with respect to activation by alkali metals and inhibition by Pi, assuming that the numbers of binding sites for AMP, alkali metals, and Pi are 4, 2, and 4, respectively. The enzyme was inhibited by concentrations of ATP and GTP below 0.1 and 0.25 mM, respectively, whereas activation of the enzyme was observed at ATP and GTP concentrations above 0.4 and 1.5 mM, respectively. These unusual kinetics with respect to ATP and GTP could be also accounted for by assuming 2 inhibitory and 4 activating sites for each ligand.  (+info)

An allosteric synthetic DNA. (3/3161)

Allosteric DNA oligonucleotides are potentially useful diagnostic reagents. Here we develop a model system for the study of allosteric interactions in DNAs. A DNA that binds either Cibacron blue or cholic acid was isolated and partially characterized. Isolation was performed using a multi-stage SELEX. First, short oligos that bind either Cibacron blue or cholic acid were enriched from random oligonucleotide pools. Then, members of the two pools were fused to form longer oligos, which were then selected for theability to bind Cibacron blue columns and elute with cholic acid. One resulting isolate (A22) was studied. Dye- and cholate-binding functions can be separated on sequences from the 5'- and 3'-regions, respectively. Ligand-column affinity assays indicate that each domain binds only its respective ligand. However, the full-length A22 will bind either dye or cholate columns and elute with the other ligand, as if binding by the ligands is mutually exclusive. Furthermore, S1 nuclease protection assays show that Cibacron blue causes a structural change in A22 and that cholic acid inhibits this change. This system will be useful for elucidating mechanisms of allosteric interactions in synthetic DNAs.  (+info)

Heterotropic effectors exert more significant strain on monoligated than on unligated hemoglobin. (4/3161)

The effect of allosteric effectors, such as inositol hexakisphosphate and/or bezafibrate, has been investigated on the unliganded human adult hemoglobin both spectroscopically (employing electronic absorption, circular dichroism, resonance Raman, and x-ray absorption near-edge spectroscopies) and functionally (following the kinetics of the first CO binding step up to a final 4% ligand saturation degree). All data indicate that the unliganded T-state is not perturbed by the interaction with either one or both effectors, suggesting that their functional influence is only exerted when a ligand molecule is bound to the heme. This is confirmed by the observation that CO dissociation from partially liganded hemoglobin ( +info)

Dual allosteric modulation of pacemaker (f) channels by cAMP and voltage in rabbit SA node. (5/3161)

1. A Monod-Whyman-Changeux (MWC) allosteric reaction model was used in the attempt to describe the dual activation of 'pacemaker' f-channel gating subunits by voltage hyperpolarization and cyclic nucleotides. Whole-channel kinetics were described by assuming that channels are composed of two identical subunits gated independently according to the Hodgkin-Huxley (HH) equations. 2. The simple assumption that cAMP binding favours open channels was found to readily explain induction of depolarizing voltage shifts of open probability with a sigmoidal dependence on agonist concentration. 3. Voltage shifts of open probability were measured against cAMP concentration in macropatches of sino-atrial (SA) node cells; model fitting of dose-response relations yielded dissociation constants of 0.0732 and 0.4192 microM for cAMP binding to open and closed channels, respectively. The allosteric model correctly predicted the modification of the pacemaker current (If) time constant curve induced by 10 microM cAMP (13.7 mV depolarizing shift). 4. cAMP shifted deactivation more than activation rate constant curves, according to sigmoidal dose-response relations (maximal shifts of +22.3 and +13.4 mV at 10 microM cAMP, respectively); this feature was fully accounted for by allosteric interactions, and indicated that cAMP acts primarily by 'locking' f-channels in the open configuration. 5. These results provide an interpretation of the dual voltage- and cyclic nucleotide- dependence of f-channel activation.  (+info)

Coupling of the oxygen-linked interaction energy for inositol hexakisphosphate and bezafibrate binding to human HbA0. (6/3161)

The energetics of signal propagation between different functional domains (i.e. the binding sites for O2, inositol hexakisphospate (IHP), and bezafibrate (BZF)) of human HbA0 was analyzed at different heme ligation states and through the use of a stable, partially heme ligated intermediate. Present data allow three main conclusions to be drawn, and namely: (i) IHP and BZF enhance each others binding as the oxygenation proceeds, the coupling free energy going from close to zero in the deoxy state to -3.4 kJ/mol in the oxygenated form; (ii) the simultaneous presence of IHP and BZF stabilizes the hemoglobin T quaternary structure at very low O2 pressures, but as oxygenation proceeds it does not impair the transition toward the R structure, which indeed occurs also under these conditions; (iii) under room air pressure (i.e. pO2 = 150 torr), IHP and BZF together induce the formation of an asymmetric dioxygenated hemoglobin tetramer, whose features appear reminiscent of those suggested for transition state species (i.e. T- and R-like tertiary conformation(s) within a quaternary R-like structure).  (+info)

Allosteric control of three B12-dependent (class II) ribonucleotide reductases. Implications for the evolution of ribonucleotide reduction. (7/3161)

Three separate classes of ribonucleotide reductases are known, each with a distinct protein structure. One common feature of all enzymes is that a single protein generates each of the four deoxyribonucleotides. Class I and III enzymes contain an allosteric substrate specificity site capable of binding effectors (ATP or various deoxyribonucleoside triphosphates) that direct enzyme specificity. Some (but not all) enzymes contain a second allosteric site that binds only ATP or dATP. Binding of dATP to this site inhibits the activity of these enzymes. X-ray crystallography has localized the two sites within the structure of the Escherichia coli class I enzyme and identified effector-binding amino acids. Here, we have studied the regulation of three class II enzymes, one from the archaebacterium Thermoplasma acidophilum and two from eubacteria (Lactobacillus leichmannii and Thermotoga maritima). Each enzyme has an allosteric site that binds ATP or various deoxyribonucleoside triphosphates and that regulates its substrate specificity according to the same rules as for class I and III enzymes. dATP does not inhibit enzyme activity, suggesting the absence of a second active allosteric site. For the L. leichmannii and T. maritima enzymes, binding experiments also indicate the presence of only one allosteric site. Their primary sequences suggest that these enzymes lack the structural requirements for a second site. In contrast, the T. acidophilum enzyme binds dATP at two separate sites, and its sequence contains putative effector-binding amino acids for a second site. The presence of a second site without apparent physiological function leads to the hypothesis that a functional site was present early during the evolution of ribonucleotide reductases, but that its function was lost from the T. acidophilum enzyme. The other two B12 enzymes lost not only the function, but also the structural basis for the site. Also a large subgroup (Ib) of class I enzymes, but none of the investigated class III enzymes, has lost this site. This is further indirect evidence that class II and I enzymes may have arisen by divergent evolution from class III enzymes.  (+info)

Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. (8/3161)

Phosphoribosylpyrophosphate (PRPP) synthetase (PRS) superactivity is an X-linked disorder characterized by gout with overproduction of purine nucleotides and uric acid. Study of the two X-linked PRS isoforms (PRS1 and PRS2) in cells from certain affected individuals has shown selectively increased concentrations of structurally normal PRS1 transcript and isoform, suggesting that this form of the disorder involves pretranslational dysregulation of PRPS1 expression and might be more appropriately termed overactivity of normal PRS. We applied Southern and Northern blot analyses and slot blotting of nuclear runoffs to delineate the process underlying aberrant PRPS1 expression in fibroblasts and lymphoblasts from patients with overactivity of normal PRS. Neither PRPS1 amplification nor altered stability or processing of PRS1 mRNA was identified, but PRPS1 transcription was increased relative to GAPDH (3- to 4-fold normal in fibroblasts; 1.9- to 2.4-fold in lymphoblasts) and PRPS2. Nearly coordinate relative increases in each process mediating transfer of genetic information from PRPS1 transcription to maximal PRS1 isoform expression in patient fibroblasts further supported the idea that accelerated PRPS1 transcription is the major aberration leading to PRS1 overexpression. In addition, modulated relative increases in PRS activities at suboptimal Pi concentration and in rates of PRPP and purine nucleotide synthesis in intact patient fibroblasts indicate that despite an intact allosteric mechanism of regulation of PRS activity, PRPS1 transcription is a major determinant of PRPP and purine synthesis. The genetic basis of disordered PRPS1 transcription remains unresolved; normal- and patient-derived PRPS1s share nucleotide sequence identity at least 850 base pairs 5' to the consensus transcription initiation site.  (+info)

Allosteric regulation is a process that describes the way in which the binding of a molecule (known as a ligand) to an enzyme or protein at one site affects the ability of another molecule to bind to a different site on the same enzyme or protein. This interaction can either enhance (positive allosteric regulation) or inhibit (negative allosteric regulation) the activity of the enzyme or protein, depending on the nature of the ligand and its effect on the shape and/or conformation of the enzyme or protein.

In an allosteric regulatory system, the binding of the first molecule to the enzyme or protein causes a conformational change in the protein structure that alters the affinity of the second site for its ligand. This can result in changes in the activity of the enzyme or protein, allowing for fine-tuning of biochemical pathways and regulatory processes within cells.

Allosteric regulation is a fundamental mechanism in many biological systems, including metabolic pathways, signal transduction cascades, and gene expression networks. Understanding allosteric regulation can provide valuable insights into the mechanisms underlying various physiological and pathological processes, and can inform the development of novel therapeutic strategies for the treatment of disease.

An allosteric site is a distinct and separate binding site on a protein (usually an enzyme) other than the active site where the substrate binds. The binding of a molecule (known as an allosteric modulator or effector) to this site can cause a conformational change in the protein's structure, which in turn affects its activity, either by enhancing (allosteric activation) or inhibiting (allosteric inhibition) its function. This allosteric regulation allows for complex control mechanisms in biological systems and is crucial for many cellular processes.

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.

Glucose-1-phosphate adenylyltransferase, also known as ADP-glucose pyrophosphorylase or AGPase, is an enzyme that plays a crucial role in carbohydrate metabolism, specifically in the synthesis of starch. It catalyzes the reaction between ATP and glucose-1-phosphate to produce ADP-glucose and pyrophosphate. This reaction is the first committed step in the biosynthetic pathway of starch in plants, algae, and some bacteria. In humans, defects in this enzyme can lead to a rare genetic disorder called glycogen storage disease type Ib.

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.

Protein conformation refers to the specific three-dimensional shape that a protein molecule assumes due to the spatial arrangement of its constituent amino acid residues and their associated chemical groups. This complex structure is determined by several factors, including covalent bonds (disulfide bridges), hydrogen bonds, van der Waals forces, and ionic bonds, which help stabilize the protein's unique conformation.

Protein conformations can be broadly classified into two categories: primary, secondary, tertiary, and quaternary structures. The primary structure represents the linear sequence of amino acids in a polypeptide chain. The secondary structure arises from local interactions between adjacent amino acid residues, leading to the formation of recurring motifs such as α-helices and β-sheets. Tertiary structure refers to the overall three-dimensional folding pattern of a single polypeptide chain, while quaternary structure describes the spatial arrangement of multiple folded polypeptide chains (subunits) that interact to form a functional protein complex.

Understanding protein conformation is crucial for elucidating protein function, as the specific three-dimensional shape of a protein directly influences its ability to interact with other molecules, such as ligands, nucleic acids, or other proteins. Any alterations in protein conformation due to genetic mutations, environmental factors, or chemical modifications can lead to loss of function, misfolding, aggregation, and disease states like neurodegenerative disorders and cancer.

Pyruvate kinase is an enzyme that plays a crucial role in the final step of glycolysis, a process by which glucose is broken down to produce energy in the form of ATP (adenosine triphosphate). Specifically, pyruvate kinase catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), resulting in the formation of pyruvate and ATP.

There are several isoforms of pyruvate kinase found in different tissues, including the liver, muscle, and brain. The type found in red blood cells is known as PK-RBC or PK-M2. Deficiencies in pyruvate kinase can lead to a genetic disorder called pyruvate kinase deficiency, which can result in hemolytic anemia due to the premature destruction of red blood cells.

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.

Quaternary protein structure refers to the arrangement and interaction of multiple folded protein molecules in a multi-subunit complex. These subunits can be identical or different forms of the same protein or distinctly different proteins that associate to form a functional complex. The quaternary structure is held together by non-covalent interactions, such as hydrogen bonds, ionic bonds, and van der Waals forces. Understanding quaternary structure is crucial for comprehending the function, regulation, and assembly of many protein complexes involved in various cellular processes.

X-ray crystallography is a technique used in structural biology to determine the three-dimensional arrangement of atoms in a crystal lattice. In this method, a beam of X-rays is directed at a crystal and diffracts, or spreads out, into a pattern of spots called reflections. The intensity and angle of each reflection are measured and used to create an electron density map, which reveals the position and type of atoms in the crystal. This information can be used to determine the molecular structure of a compound, including its shape, size, and chemical bonds. X-ray crystallography is a powerful tool for understanding the structure and function of biological macromolecules such as proteins and nucleic acids.

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.

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.

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.

Ribonucleotide Reductases (RNRs) are enzymes that play a crucial role in DNA synthesis and repair. They catalyze the conversion of ribonucleotides to deoxyribonucleotides, which are the building blocks of DNA. This process involves the reduction of the 2'-hydroxyl group of the ribose sugar to a hydrogen, resulting in the formation of deoxyribose.

RNRs are highly regulated and exist in various forms across different species. They are divided into three classes (I, II, and III) based on their structure, mechanism, and cofactor requirements. Class I RNRs are further divided into two subclasses (Ia and Ib), which differ in their active site architecture and regulation.

Class Ia RNRs, found in eukaryotes and some bacteria, contain a stable tyrosyl radical that acts as the catalytic center for hydrogen abstraction. Class Ib RNRs, found in many bacteria, use a pair of iron centers to perform the same function. Class II RNRs are present in some bacteria and archaea and utilize adenosine triphosphate (ATP) as a cofactor for reduction. Class III RNRs, found in anaerobic bacteria and archaea, use a unique mechanism involving a radical S-adenosylmethionine (SAM) cofactor to facilitate the reduction reaction.

RNRs are essential for DNA replication and repair, and their dysregulation has been linked to various diseases, including cancer and neurodegenerative disorders. Therefore, understanding the structure, function, and regulation of RNRs is of great interest in biochemistry, molecular biology, and medicine.

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.

I believe there might be a slight misunderstanding in your question. "Glyceric acid" is not a widely recognized or established term in medicine or biochemistry. However, glyceric acid can refer to a specific compound with the chemical formula C3H8O4, also known as 2,3-dihydroxypropanoid acid or glycerol-3-phosphate when phosphorylated.

Glyceric acid is an organic compound that plays a crucial role in cellular metabolism, particularly in energy production pathways such as glycolysis and gluconeogenesis. It can be formed from the reduction of dihydroxyacetone phosphate (a glycolytic intermediate) or through the oxidation of glycerol.

If you were referring to a different term or concept, please provide more context so I can give a more accurate answer.

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.

Bithionol is an oral antiparasitic medication that has been used to treat infections caused by certain types of tapeworms, such as Paragonimus westermani (lung fluke) and Fasciolopsis buski (intestinal fluke). It works by inhibiting the metabolic processes of the parasites, which helps to eliminate them from the body.

Bithionol is no longer commonly used due to the availability of safer and more effective antiparasitic drugs. Its use may be associated with several side effects, including nausea, vomiting, diarrhea, abdominal pain, dizziness, and skin rashes. In some cases, it may also cause liver damage or allergic reactions.

It is important to note that bithionol should only be used under the supervision of a healthcare professional, as its use requires careful monitoring and dosage adjustment based on the patient's response to treatment.

Aspartate carbamoyltransferase (ACT) is a crucial enzyme in the urea cycle, which is the biochemical pathway responsible for the elimination of excess nitrogen waste from the body. This enzyme catalyzes the second step of the urea cycle, where it facilitates the transfer of a carbamoyl group from carbamoyl phosphate to aspartic acid, forming N-acetylglutamic semialdehyde and releasing phosphate in the process.

The reaction catalyzed by aspartate carbamoyltransferase is as follows:

Carbamoyl phosphate + L-aspartate → N-acetylglutamic semialdehyde + P\_i + CO\_2

This enzyme plays a critical role in maintaining nitrogen balance and preventing the accumulation of toxic levels of ammonia in the body. Deficiencies or mutations in aspartate carbamoyltransferase can lead to serious metabolic disorders, such as citrullinemia and hyperammonemia, which can have severe neurological consequences if left untreated.

A ligand, in the context of biochemistry and medicine, is a molecule that binds to a specific site on a protein or a larger biomolecule, such as an enzyme or a receptor. This binding interaction can modify the function or activity of the target protein, either activating it or inhibiting it. Ligands can be small molecules, like hormones or neurotransmitters, or larger structures, like antibodies. The study of ligand-protein interactions is crucial for understanding cellular processes and developing drugs, as many therapeutic compounds function by binding to specific targets within the body.

'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.

Protein multimerization refers to the process where multiple protein subunits assemble together to form a complex, repetitive structure called a multimer or oligomer. This can involve the association of identical or similar protein subunits through non-covalent interactions such as hydrogen bonding, ionic bonding, and van der Waals forces. The resulting multimeric structures can have various shapes, sizes, and functions, including enzymatic activity, transport, or structural support. Protein multimerization plays a crucial role in many biological processes and is often necessary for the proper functioning of proteins within cells.

Chorismate mutase is an important enzyme in the biosynthetic pathway of aromatic amino acids in bacteria, fungi, and plants. This enzyme catalyzes the conversion of chorismate to prephenate, which is a key step in the synthesis of phenylalanine, tyrosine, and tryptophan.

The reaction catalyzed by chorismate mutase is as follows:

chorismate → prephenate

Inhibition of this enzyme has been explored as a potential target for the development of antibiotics and herbicides, as interrupting the synthesis of aromatic amino acids can be lethal to bacteria and plants. In humans, the equivalent reaction is catalyzed by a different set of enzymes, so chorismate mutase inhibitors are not expected to have toxic effects on human cells.

I'm sorry for any confusion, but "Fructosediphosphates" is not a recognized term in medicine or biochemistry. It's possible there may be a spelling mistake or misunderstanding in the term you're looking for.

If you meant "Fructose 1,6-bisphosphate," that is a key intermediate in carbohydrate metabolism. It's formed from fructose 6-phosphate in the process of glucose breakdown (glycolysis) and is then used in the generation of energy through the citric acid cycle.

If these terms are not what you were looking for, could you please provide more context or check the spelling? I'm here to help!

Glutamate Dehydrogenase (GLDH or GDH) is a mitochondrial enzyme that plays a crucial role in the metabolism of amino acids, particularly within liver and kidney tissues. It catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate, which links amino acid metabolism with the citric acid cycle and energy production. This enzyme is significant in clinical settings as its levels in blood serum can be used as a diagnostic marker for diseases that damage liver or kidney cells, since these cells release GLDH into the bloodstream upon damage.

Glycerol kinase is an enzyme that plays a crucial role in the metabolism of glycerol, which is a simple carbohydrate. The enzyme catalyzes the conversion of glycerol to glycerol-3-phosphate by transferring a phosphate group from ATP to glycerol. This reaction is an essential step in the metabolic pathway that leads to the formation of glucose or other energy-rich compounds in the body.

There are two main forms of glycerol kinase found in humans, designated as GK1 and GK2. GK1 is primarily expressed in the liver, while GK2 is found in various tissues, including the brain, heart, and muscles. Deficiencies in glycerol kinase can lead to metabolic disorders such as hyperglycerolemia, which is characterized by high levels of glycerol in the blood.

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.

Uridine Monophosphate (UMP) is a nucleotide that is a constituent of RNA (Ribonucleic Acid). It consists of a nitrogenous base called Uridine, linked to a sugar molecule (ribose) and a phosphate group. UMP plays a crucial role in various biochemical reactions within the body, including energy transfer and cellular metabolism. It is also involved in the synthesis of other nucleotides and serves as an important precursor in the production of genetic material during cell division.

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.

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.

A protein subunit refers to a distinct and independently folding polypeptide chain that makes up a larger protein complex. Proteins are often composed of multiple subunits, which can be identical or different, that come together to form the functional unit of the protein. These subunits can interact with each other through non-covalent interactions such as hydrogen bonds, ionic bonds, and van der Waals forces, as well as covalent bonds like disulfide bridges. The arrangement and interaction of these subunits contribute to the overall structure and function of the protein.

Adenosine monophosphate (AMP) is a nucleotide that is the monophosphate ester of adenosine, consisting of the nitrogenous base adenine attached to the 1' carbon atom of ribose via a β-N9-glycosidic bond, which in turn is esterified to a phosphate group. It is an important molecule in biological systems as it plays a key role in cellular energy transfer and storage, serving as a precursor to other nucleotides such as ADP and ATP. AMP is also involved in various signaling pathways and can act as a neurotransmitter in the central nervous system.

Phosphofructokinase-1 (PFK-1) is a rate-limiting enzyme in the glycolytic pathway, which is the metabolic pathway that converts glucose into pyruvate, producing ATP and NADH as energy currency for the cell. PFK-1 plays a crucial role in regulating the rate of glycolysis by catalyzing the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, using ATP as the phosphate donor.

PFK-1 is allosterically regulated by various metabolites, such as AMP, ADP, and ATP, which act as positive or negative effectors of the enzyme's activity. For example, an increase in the intracellular concentration of AMP or ADP can activate PFK-1, promoting glycolysis and energy production, while an increase in ATP levels can inhibit the enzyme's activity, conserving glucose for use under conditions of low energy demand.

Deficiencies in PFK-1 can lead to a rare genetic disorder called Tarui's disease or glycogen storage disease type VII, which is characterized by exercise intolerance, muscle cramps, and myoglobinuria (the presence of myoglobin in the urine due to muscle damage).

Molecular Dynamics (MD) simulation is a computational method used in the field of molecular modeling and molecular physics. It involves simulating the motions and interactions of atoms and molecules over time, based on classical mechanics or quantum mechanics. In MD simulations, the equations of motion for each atom are repeatedly solved, allowing researchers to study the dynamic behavior of molecular systems, such as protein folding, ligand-protein binding, and chemical reactions. These simulations provide valuable insights into the structural and functional properties of biological macromolecules at the atomic level, and have become an essential tool in modern drug discovery and development.

Aromatic amino acids are a specific type of amino acids that contain an aromatic ring in their side chain. The three aromatic amino acids are phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp). These amino acids play important roles in various biological processes, including protein structure and function, neurotransmission, and enzyme catalysis.

The aromatic ring in these amino acids is composed of a planar six-membered carbon ring that contains alternating double bonds. This structure gives the side chains unique chemical properties, such as their ability to absorb ultraviolet light and participate in stacking interactions with other aromatic residues. These interactions can contribute to the stability and function of proteins and other biological molecules.

It's worth noting that while most amino acids are classified as either "hydrophobic" or "hydrophilic," depending on their chemical properties, aromatic amino acids exhibit characteristics of both groups. They can form hydrogen bonds with polar residues and also engage in hydrophobic interactions with nonpolar residues, making them versatile building blocks for protein structure and function.

Secondary protein structure refers to the local spatial arrangement of amino acid chains in a protein, typically described as regular repeating patterns held together by hydrogen bonds. The two most common types of secondary structures are the alpha-helix (α-helix) and the beta-pleated sheet (β-sheet). In an α-helix, the polypeptide chain twists around itself in a helical shape, with each backbone atom forming a hydrogen bond with the fourth amino acid residue along the chain. This forms a rigid rod-like structure that is resistant to bending or twisting forces. In β-sheets, adjacent segments of the polypeptide chain run parallel or antiparallel to each other and are connected by hydrogen bonds, forming a pleated sheet-like arrangement. These secondary structures provide the foundation for the formation of tertiary and quaternary protein structures, which determine the overall three-dimensional shape and function of the protein.

Dimerization is a process in which two molecules, usually proteins or similar structures, bind together to form a larger complex. This can occur through various mechanisms, such as the formation of disulfide bonds, hydrogen bonding, or other non-covalent interactions. Dimerization can play important roles in cell signaling, enzyme function, and the regulation of gene expression.

In the context of medical research and therapy, dimerization is often studied in relation to specific proteins that are involved in diseases such as cancer. For example, some drugs have been developed to target and inhibit the dimerization of certain proteins, with the goal of disrupting their function and slowing or stopping the progression of the disease.

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.

Glucose-6-phosphate (G6P) is a vital intermediate compound in the metabolism of glucose, which is a simple sugar that serves as a primary source of energy for living organisms. G6P plays a critical role in both glycolysis and gluconeogenesis pathways, contributing to the regulation of blood glucose levels and energy production within cells.

In biochemistry, glucose-6-phosphate is defined as:

A hexose sugar phosphate ester formed by the phosphorylation of glucose at the 6th carbon atom by ATP in a reaction catalyzed by the enzyme hexokinase or glucokinase. This reaction is the first step in both glycolysis and glucose storage (glycogen synthesis) processes, ensuring that glucose can be effectively utilized for energy production or stored for later use.

G6P serves as a crucial metabolic branch point, leading to various pathways such as:

1. Glycolysis: In the presence of sufficient ATP and NAD+ levels, G6P is further metabolized through glycolysis to generate pyruvate, which enters the citric acid cycle for additional energy production in the form of ATP, NADH, and FADH2.
2. Gluconeogenesis: During periods of low blood glucose levels, G6P can be synthesized back into glucose through the gluconeogenesis pathway, primarily occurring in the liver and kidneys. This process helps maintain stable blood glucose concentrations and provides energy to cells when dietary intake is insufficient.
3. Pentose phosphate pathway (PPP): A portion of G6P can be shunted into the PPP, an alternative metabolic route that generates NADPH, ribose-5-phosphate for nucleotide synthesis, and erythrose-4-phosphate for aromatic amino acid production. The PPP is essential in maintaining redox balance within cells and supporting biosynthetic processes.

Overall, glucose-6-phosphate plays a critical role as a central metabolic intermediate, connecting various pathways to regulate energy homeostasis, redox balance, and biosynthesis in response to cellular demands and environmental cues.

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.

Nucleotidyltransferases are a class of enzymes that catalyze the transfer of nucleotides to an acceptor molecule, such as RNA or DNA. These enzymes play crucial roles in various biological processes, including DNA replication, repair, and recombination, as well as RNA synthesis and modification.

The reaction catalyzed by nucleotidyltransferases typically involves the donation of a nucleoside triphosphate (NTP) to an acceptor molecule, resulting in the formation of a phosphodiester bond between the nucleotides. The reaction can be represented as follows:

NTP + acceptor → NMP + pyrophosphate

where NTP is the nucleoside triphosphate donor and NMP is the nucleoside monophosphate product.

There are several subclasses of nucleotidyltransferases, including polymerases, ligases, and terminases. These enzymes have distinct functions and substrate specificities, but all share the ability to transfer nucleotides to an acceptor molecule.

Examples of nucleotidyltransferases include DNA polymerase, RNA polymerase, reverse transcriptase, telomerase, and ligase. These enzymes are essential for maintaining genome stability and function, and their dysregulation has been implicated in various diseases, including cancer and neurodegenerative disorders.

Phosphoglycerate Dehydrogenase (PGDH) is a critical enzyme in the metabolic pathway of glycolysis and serine synthesis. It catalyzes the first step in the serine synthesis pathway, where 3-phosphoglycerate is converted to 3-phosphohydroxypyruvate, while also reducing nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide hydride (NADH). This enzyme plays a significant role in cellular metabolism and has been linked to various diseases, including cancer, when its activity is dysregulated.

Biocatalysis is the use of living organisms or their components, such as enzymes, to accelerate chemical reactions. In other words, it is the process by which biological systems, including cells, tissues, and organs, catalyze chemical transformations. Biocatalysts, such as enzymes, can increase the rate of a reaction by lowering the activation energy required for the reaction to occur. They are highly specific and efficient, making them valuable tools in various industries, including pharmaceuticals, food and beverage, and biofuels.

In medicine, biocatalysis is used in the production of drugs, such as antibiotics and hormones, as well as in diagnostic tests. Enzymes are also used in medical treatments, such as enzyme replacement therapy for genetic disorders that affect enzyme function. Overall, biocatalysis plays a critical role in many areas of medicine and healthcare.

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.

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.

I'm sorry for any confusion, but "thermodynamics" is not a term that has a specific medical definition. It is a branch of physics that deals with the relationships between heat and other forms of energy. However, the principles of thermodynamics can be applied to biological systems, including those in the human body, such as in the study of metabolism or muscle function. But in a medical context, "thermodynamics" would not be a term used independently as a diagnosis, treatment, or any medical condition.

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.

Molecular conformation, also known as spatial arrangement or configuration, refers to the specific three-dimensional shape and orientation of atoms that make up a molecule. It describes the precise manner in which bonds between atoms are arranged around a molecular framework, taking into account factors such as bond lengths, bond angles, and torsional angles.

Conformational isomers, or conformers, are different spatial arrangements of the same molecule that can interconvert without breaking chemical bonds. These isomers may have varying energies, stability, and reactivity, which can significantly impact a molecule's biological activity and function. Understanding molecular conformation is crucial in fields such as drug design, where small changes in conformation can lead to substantial differences in how a drug interacts with its target.

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.

Hydrogen bonding is not a medical term per se, but it is a fundamental concept in chemistry and biology that is relevant to the field of medicine. Here's a general definition:

Hydrogen bonding is a type of attractive force between molecules or within a molecule, which occurs when a hydrogen atom is bonded to a highly electronegative atom (like nitrogen, oxygen, or fluorine) and is then attracted to another electronegative atom. This attraction results in the formation of a partially covalent bond known as a "hydrogen bond."

In biological systems, hydrogen bonding plays a crucial role in the structure and function of many biomolecules, such as DNA, proteins, and carbohydrates. For example, the double helix structure of DNA is stabilized by hydrogen bonds between complementary base pairs (adenine-thymine and guanine-cytosine). Similarly, the three-dimensional structure of proteins is maintained by a network of hydrogen bonds that help to determine their function.

In medical contexts, hydrogen bonding can be relevant in understanding drug-receptor interactions, where hydrogen bonds between a drug molecule and its target protein can enhance the binding affinity and specificity of the interaction, leading to more effective therapeutic outcomes.

A chemical model is a simplified representation or description of a chemical system, based on the laws of chemistry and physics. It is used to explain and predict the behavior of chemicals and chemical reactions. Chemical models can take many forms, including mathematical equations, diagrams, and computer simulations. They are often used in research, education, and industry to understand complex chemical processes and develop new products and technologies.

For example, a chemical model might be used to describe the way that atoms and molecules interact in a particular reaction, or to predict the properties of a new material. Chemical models can also be used to study the behavior of chemicals at the molecular level, such as how they bind to each other or how they are affected by changes in temperature or pressure.

It is important to note that chemical models are simplifications of reality and may not always accurately represent every aspect of a chemical system. They should be used with caution and validated against experimental data whenever possible.

'Escherichia coli (E. coli) proteins' refer to the various types of proteins that are produced and expressed by the bacterium Escherichia coli. These proteins play a critical role in the growth, development, and survival of the organism. They are involved in various cellular processes such as metabolism, DNA replication, transcription, translation, repair, and regulation.

E. coli is a gram-negative, facultative anaerobe that is commonly found in the intestines of warm-blooded organisms. It is widely used as a model organism in scientific research due to its well-studied genetics, rapid growth, and ability to be easily manipulated in the laboratory. As a result, many E. coli proteins have been identified, characterized, and studied in great detail.

Some examples of E. coli proteins include enzymes involved in carbohydrate metabolism such as lactase, sucrase, and maltose; proteins involved in DNA replication such as the polymerases, single-stranded binding proteins, and helicases; proteins involved in transcription such as RNA polymerase and sigma factors; proteins involved in translation such as ribosomal proteins, tRNAs, and aminoacyl-tRNA synthetases; and regulatory proteins such as global regulators, two-component systems, and transcription factors.

Understanding the structure, function, and regulation of E. coli proteins is essential for understanding the basic biology of this important organism, as well as for developing new strategies for combating bacterial infections and improving industrial processes involving bacteria.

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.

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.

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.

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.

Hemoglobin (Hb or Hgb) is the main oxygen-carrying protein in the red blood cells, which are responsible for delivering oxygen throughout the body. It is a complex molecule made up of four globin proteins and four heme groups. Each heme group contains an iron atom that binds to one molecule of oxygen. Hemoglobin plays a crucial role in the transport of oxygen from the lungs to the body's tissues, and also helps to carry carbon dioxide back to the lungs for exhalation.

There are several types of hemoglobin present in the human body, including:

* Hemoglobin A (HbA): This is the most common type of hemoglobin, making up about 95-98% of total hemoglobin in adults. It consists of two alpha and two beta globin chains.
* Hemoglobin A2 (HbA2): This makes up about 1.5-3.5% of total hemoglobin in adults. It consists of two alpha and two delta globin chains.
* Hemoglobin F (HbF): This is the main type of hemoglobin present in fetal life, but it persists at low levels in adults. It consists of two alpha and two gamma globin chains.
* Hemoglobin S (HbS): This is an abnormal form of hemoglobin that can cause sickle cell disease when it occurs in the homozygous state (i.e., both copies of the gene are affected). It results from a single amino acid substitution in the beta globin chain.
* Hemoglobin C (HbC): This is another abnormal form of hemoglobin that can cause mild to moderate hemolytic anemia when it occurs in the homozygous state. It results from a different single amino acid substitution in the beta globin chain than HbS.

Abnormal forms of hemoglobin, such as HbS and HbC, can lead to various clinical disorders, including sickle cell disease, thalassemia, and other hemoglobinopathies.

Nucleotides are the basic structural units of nucleic acids, such as DNA and RNA. They consist of a nitrogenous base (adenine, guanine, cytosine, thymine or uracil), a pentose sugar (ribose in RNA and deoxyribose in DNA) and one to three phosphate groups. Nucleotides are linked together by phosphodiester bonds between the sugar of one nucleotide and the phosphate group of another, forming long chains known as polynucleotides. The sequence of these nucleotides determines the genetic information carried in DNA and RNA, which is essential for the functioning, reproduction and survival of all living organisms.

An amino acid substitution is a type of mutation in which one amino acid in a protein is replaced by another. This occurs when there is a change in the DNA sequence that codes for a particular amino acid in a protein. The genetic code is redundant, meaning that most amino acids are encoded by more than one codon (a sequence of three nucleotides). As a result, a single base pair change in the DNA sequence may not necessarily lead to an amino acid substitution. However, if a change does occur, it can have a variety of effects on the protein's structure and function, depending on the nature of the substituted amino acids. Some substitutions may be harmless, while others may alter the protein's activity or stability, leading to disease.

Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.

The Phosphoenolpyruvate (PEP) sugar phosphotransferase system (PTS) is not exactly a "sugar," but rather a complex molecular machinery used by certain bacteria for the transport and phosphorylation of sugars. The PTS system is a major carbohydrate transport system in many gram-positive and gram-negative bacteria, which allows them to take up and metabolize various sugars for energy and growth.

The PTS system consists of several protein components, including the enzyme I (EI), histidine phosphocarrier protein (HPr), and sugar-specific enzymes II (EII). The process begins when PEP transfers a phosphate group to EI, which then passes it on to HPr. The phosphorylated HPr then interacts with the sugar-specific EII complex, which is composed of two domains: the membrane-associated domain (EIIA) and the periplasmic domain (EIIC).

When a sugar molecule binds to the EIIC domain, it induces a conformational change that allows the phosphate group from HPr to be transferred to the sugar. This phosphorylation event facilitates the translocation of the sugar across the membrane and into the cytoplasm, where it undergoes further metabolic reactions.

In summary, the Phosphoenolpyruvate Sugar Phosphotransferase System (PEP-PTS) is a bacterial transport system that utilizes phosphoryl groups from phosphoenolpyruvate to facilitate the uptake and phosphorylation of sugars, allowing bacteria to efficiently metabolize and utilize various carbon sources for energy and growth.

Protein engineering is a branch of molecular biology that involves the modification of proteins to achieve desired changes in their structure and function. This can be accomplished through various techniques, including site-directed mutagenesis, gene shuffling, directed evolution, and rational design. The goal of protein engineering may be to improve the stability, activity, specificity, or other properties of a protein for therapeutic, diagnostic, industrial, or research purposes. It is an interdisciplinary field that combines knowledge from genetics, biochemistry, structural biology, and computational modeling.

Enzyme stability refers to the ability of an enzyme to maintain its structure and function under various environmental conditions, such as temperature, pH, and the presence of denaturants or inhibitors. A stable enzyme retains its activity and conformation over time and across a range of conditions, making it more suitable for industrial and therapeutic applications.

Enzymes can be stabilized through various methods, including chemical modification, immobilization, and protein engineering. Understanding the factors that affect enzyme stability is crucial for optimizing their use in biotechnology, medicine, and research.

Guanosine triphosphate (GTP) is a nucleotide that plays a crucial role in various cellular processes, such as protein synthesis, signal transduction, and regulation of enzymatic activities. It serves as an energy currency, similar to adenosine triphosphate (ATP), and undergoes hydrolysis to guanosine diphosphate (GDP) or guanosine monophosphate (GMP) to release energy required for these processes. GTP is also a precursor for the synthesis of other essential molecules, including RNA and certain signaling proteins. Additionally, it acts as a molecular switch in many intracellular signaling pathways by binding and activating specific GTPase proteins.

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.

Glycogen is a complex carbohydrate that serves as the primary form of energy storage in animals, fungi, and bacteria. It is a polysaccharide consisting of long, branched chains of glucose molecules linked together by glycosidic bonds. Glycogen is stored primarily in the liver and muscles, where it can be quickly broken down to release glucose into the bloodstream during periods of fasting or increased metabolic demand.

In the liver, glycogen plays a crucial role in maintaining blood glucose levels by releasing glucose when needed, such as between meals or during exercise. In muscles, glycogen serves as an immediate energy source for muscle contractions during intense physical activity. The ability to store and mobilize glycogen is essential for the proper functioning of various physiological processes, including athletic performance, glucose homeostasis, and overall metabolic health.

Aspartic acid is an α-amino acid with the chemical formula HO2CCH(NH2)CO2H. It is one of the twenty standard amino acids, and it is a polar, negatively charged, and hydrophilic amino acid. In proteins, aspartic acid usually occurs in its ionized form, aspartate, which has a single negative charge.

Aspartic acid plays important roles in various biological processes, including metabolism, neurotransmitter synthesis, and energy production. It is also a key component of many enzymes and proteins, where it often contributes to the formation of ionic bonds and helps stabilize protein structure.

In addition to its role as a building block of proteins, aspartic acid is also used in the synthesis of other important biological molecules, such as nucleotides, which are the building blocks of DNA and RNA. It is also a component of the dipeptide aspartame, an artificial sweetener that is widely used in food and beverages.

Like other amino acids, aspartic acid is essential for human health, but it cannot be synthesized by the body and must be obtained through the diet. Foods that are rich in aspartic acid include meat, poultry, fish, dairy products, eggs, legumes, and some fruits and vegetables.

Histidine is an essential amino acid, meaning it cannot be synthesized by the human body and must be obtained through dietary sources. Its chemical formula is C6H9N3O2. Histidine plays a crucial role in several physiological processes, including:

1. Protein synthesis: As an essential amino acid, histidine is required for the production of proteins, which are vital components of various tissues and organs in the body.

2. Hemoglobin synthesis: Histidine is a key component of hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. The imidazole side chain of histidine acts as a proton acceptor/donor, facilitating the release and uptake of oxygen by hemoglobin.

3. Acid-base balance: Histidine is involved in maintaining acid-base homeostasis through its role in the biosynthesis of histamine, which is a critical mediator of inflammatory responses and allergies. The decarboxylation of histidine results in the formation of histamine, which can increase vascular permeability and modulate immune responses.

4. Metal ion binding: Histidine has a high affinity for metal ions such as zinc, copper, and iron. This property allows histidine to participate in various enzymatic reactions and maintain the structural integrity of proteins.

5. Antioxidant defense: Histidine-containing dipeptides, like carnosine and anserine, have been shown to exhibit antioxidant properties by scavenging reactive oxygen species (ROS) and chelating metal ions. These compounds may contribute to the protection of proteins and DNA from oxidative damage.

Dietary sources of histidine include meat, poultry, fish, dairy products, and wheat germ. Histidine deficiency is rare but can lead to growth retardation, anemia, and impaired immune function.

Oxygen is a colorless, odorless, tasteless gas that constitutes about 21% of the earth's atmosphere. It is a crucial element for human and most living organisms as it is vital for respiration. Inhaled oxygen enters the lungs and binds to hemoglobin in red blood cells, which carries it to tissues throughout the body where it is used to convert nutrients into energy and carbon dioxide, a waste product that is exhaled.

Medically, supplemental oxygen therapy may be provided to patients with conditions such as chronic obstructive pulmonary disease (COPD), pneumonia, heart failure, or other medical conditions that impair the body's ability to extract sufficient oxygen from the air. Oxygen can be administered through various devices, including nasal cannulas, face masks, and ventilators.

Glycogen synthase is an enzyme (EC 2.4.1.11) that plays a crucial role in the synthesis of glycogen, a polysaccharide that serves as the primary storage form of glucose in animals, fungi, and bacteria. This enzyme catalyzes the transfer of glucosyl residues from uridine diphosphate glucose (UDP-glucose) to the non-reducing end of an growing glycogen chain, thereby elongating it.

Glycogen synthase is regulated by several mechanisms, including allosteric regulation and covalent modification. The activity of this enzyme is inhibited by high levels of intracellular glucose-6-phosphate (G6P) and activated by the binding of glycogen or proteins that bind to glycogen, such as glycogenin. Phosphorylation of glycogen synthase by protein kinases, like glycogen synthase kinase-3 (GSK3), also reduces its activity, while dephosphorylation by protein phosphatases enhances it.

The regulation of glycogen synthase is critical for maintaining glucose homeostasis and energy balance in the body. Dysregulation of this enzyme has been implicated in several metabolic disorders, including type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

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.

Ion channel gating refers to the process by which ion channels in cell membranes open and close in response to various stimuli, allowing ions such as sodium, potassium, and calcium to flow into or out of the cell. This movement of ions is crucial for many physiological processes, including the generation and transmission of electrical signals in nerve cells, muscle contraction, and the regulation of hormone secretion.

Ion channel gating can be regulated by various factors, including voltage changes across the membrane (voltage-gated channels), ligand binding (ligand-gated channels), mechanical stress (mechanosensitive channels), or other intracellular signals (second messenger-gated channels). The opening and closing of ion channels are highly regulated and coordinated processes that play a critical role in maintaining the proper functioning of cells and organ systems.

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.

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 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.

Fluorescence spectrometry is a type of analytical technique used to investigate the fluorescent properties of a sample. It involves the measurement of the intensity of light emitted by a substance when it absorbs light at a specific wavelength and then re-emits it at a longer wavelength. This process, known as fluorescence, occurs because the absorbed energy excites electrons in the molecules of the substance to higher energy states, and when these electrons return to their ground state, they release the excess energy as light.

Fluorescence spectrometry typically measures the emission spectrum of a sample, which is a plot of the intensity of emitted light versus the wavelength of emission. This technique can be used to identify and quantify the presence of specific fluorescent molecules in a sample, as well as to study their photophysical properties.

Fluorescence spectrometry has many applications in fields such as biochemistry, environmental science, and materials science. For example, it can be used to detect and measure the concentration of pollutants in water samples, to analyze the composition of complex biological mixtures, or to study the properties of fluorescent nanomaterials.

Protein folding is the process by which a protein molecule naturally folds into its three-dimensional structure, following the synthesis of its amino acid chain. This complex process is determined by the sequence and properties of the amino acids, as well as various environmental factors such as temperature, pH, and the presence of molecular chaperones. The final folded conformation of a protein is crucial for its proper function, as it enables the formation of specific interactions between different parts of the molecule, which in turn define its biological activity. Protein misfolding can lead to various diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

Proteins are complex, large molecules that play critical roles in the body's functions. They are made up of amino acids, which are organic compounds that are the building blocks of proteins. Proteins are required for the structure, function, and regulation of the body's tissues and organs. They are essential for the growth, repair, and maintenance of body tissues, and they play a crucial role in many biological processes, including metabolism, immune response, and cellular signaling. Proteins can be classified into different types based on their structure and function, such as enzymes, hormones, antibodies, and structural proteins. They are found in various foods, especially animal-derived products like meat, dairy, and eggs, as well as plant-based sources like beans, nuts, and grains.

Macromolecular substances, also known as macromolecules, are large, complex molecules made up of repeating subunits called monomers. These substances are formed through polymerization, a process in which many small molecules combine to form a larger one. Macromolecular substances can be naturally occurring, such as proteins, DNA, and carbohydrates, or synthetic, such as plastics and synthetic fibers.

In the context of medicine, macromolecular substances are often used in the development of drugs and medical devices. For example, some drugs are designed to bind to specific macromolecules in the body, such as proteins or DNA, in order to alter their function and produce a therapeutic effect. Additionally, macromolecular substances may be used in the creation of medical implants, such as artificial joints and heart valves, due to their strength and durability.

It is important for healthcare professionals to have an understanding of macromolecular substances and how they function in the body, as this knowledge can inform the development and use of medical treatments.

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.

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.

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.

N-Methylscopolamine is a anticholinergic drug, which means it blocks the action of acetylcholine, a neurotransmitter in the body. It is a derivative of scopolamine and is used to treat various conditions such as gastrointestinal disorders (such as gastritis, peptic ulcer), Parkinson's disease, motion sickness, and to reduce saliva production during surgical or diagnostic procedures.

It works by blocking the muscarinic receptors in the nervous system, which leads to a decrease in the secretion of fluids (such as saliva, sweat, stomach acid) and decreased muscle contractions in the gastrointestinal tract. N-Methylscopolamine can also cause side effects such as dizziness, dry mouth, blurred vision, and difficulty urinating.

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.

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.

In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule ... Ensemble models of allosteric regulation enumerate an allosteric system's statistical ensemble as a function of its potential ... allosteric regulation is also expected to play an increasing role in drug discovery and bioengineering. The AlloSteric Database ... whereas those that decrease the protein's activity are called allosteric inhibitors. Allosteric regulations are a natural ...
Stadtman, E.R. (1966). "Allosteric regulation of enzyme activity". Advances in Enzymology and Related Areas of Molecular ... ISBN 978-0-374-29912-5. Sauro, H.M. (2017). "Control and regulation of pathways via negative feedback". Journal of the Royal ... Monod, J.; Changeux, J.-P.; Jacob, F. (1963). "Allosteric Proteins and Cellular Control Systems". J. Mol. Biol. 6 (4): 306-329 ... Nonetheless, despite these positive assessments by leading biochemists of the time, the discovery of feedback regulation is ...
Allosteric regulation is the binding of an effector to a site on the protein other than the active site, causing a ... Jurica MS, Mesecar A, Heath PJ, Shi W, Nowak T, Stoddard BL (February 1998). "The allosteric regulation of pyruvate kinase by ... Valentini G, Chiarelli L, Fortin R, Speranza ML, Galizzi A, Mattevi A (June 2000). "The allosteric regulation of pyruvate ... Dombrauckas JD, Santarsiero BD, Mesecar AD (July 2005). "Structural basis for tumor pyruvate kinase M2 allosteric regulation ...
Allosteric regulation by metabolites. The regulation of the citric acid cycle is largely determined by product inhibition and ... There is no known allosteric mechanism that can account for large changes in reaction rate from an allosteric effector whose ... Regulation by calcium. Calcium is also used as a regulator in the citric acid cycle. Calcium levels in the mitochondrial matrix ... Stryer L, Berg JM, Tymoczko JL (2002). "Section 18.6: The Regulation of Cellular Respiration Is Governed Primarily by the Need ...
A common mechanism is allosteric regulation. This is when a substrate binds a repressor protein and causes it to undergo a ...
In biochemistry, allosteric regulation (or allosteric control) is the regulation of a protein by binding an effector molecule ... has become another good example of allosteric regulation. The kinetic properties of allosteric enzymes are often explained in ... whereas those that decrease the protein's activity are called allosteric inhibitors.[citation needed] Allosteric regulations ... Allosteric regulation is also particularly important in the cell's ability to adjust enzyme activity. The term allostery comes ...
Kern, Dorothee; Zuiderweg, Erik RP (2003). "The role of dynamics in allosteric regulation". Current Opinion in Structural ... Kern, Dorothee; Zuiderweg, Erik RP (2003). "The role of dynamics in allosteric regulation". Current Opinion in Structural ... of her research include the activation of proteins and changes in protein shape and the connection to allosteric regulation. ...
Valentini G, Chiarelli L, Fortin R, Speranza ML, Galizzi A, Mattevi A (June 2000). "The allosteric regulation of pyruvate ... Localization In animals, regulation of blood glucose levels by the pancreas in conjunction with the liver is a vital part of ... The details of regulation for some enzymes are highly conserved between species, whereas others vary widely. Gene Expression: ... Thus, the relevance of ATP as an allosteric effector is questionable. An increase in AMP is a consequence of a decrease in ...
Giladi, Moshe; Khananshvili, Daniel (2013-01-01). "Molecular Determinants of Allosteric Regulation in NCX Proteins". Sodium ... Allosteric activation of NCX involves the binding of cytosolic Ca2+ to regulatory domains CBD1 and CBD2. The generalized ... A large central loop is not required for transport function and plays a role in regulation. In the preferred 9 TMS model for ... DiPolo, Reinaldo; Beaugé, Luis (2006-01-01). "Sodium/calcium exchanger: influence of metabolic regulation on ion carrier ...
Mechanisms of Cooperativity and Allosteric Regulation in Proteins. Cambridge. Cambridge University Press ISBN 0-521-38648-9 ...
Differences occur in ligand binding and allosteric regulation. Myoglobin is found in vertebrate muscle cells and is a water- ... ISBN 1-57259-153-6. Frazer, David M.; Anderson, Gregory J. (March 2014). "The regulation of iron transport: The Regulation of ...
... allosteric regulation]. RopB regulation speB is a key determinant in the expression of the speB proteinase which is a primary ... erythrogenic toxins allosteric regulation alpha helix PDB: 5DL2​; Makthal N, Gavagan M, Do H, Olsen RJ, Musser JM, Kumaraswami ... Functional studies suggest that the ropB multigene regulon is responsible for not only global regulation of virulence but also ... The location of the ropB gene is directly and sequentially proximal to the subject of its transcriptional regulation (speB) ...
The concerted model (the Monod, Wyman and Changeux (MWC) model) of allosteric regulation requires all subunits to be in the ... Interconversion of morpheein forms can be a structural basis for allosteric regulation, an idea noted many years ago, and later ... De Riel, Jon K.; Paulus, Henry (1978). "Subunit dissociation in the allosteric regulation of glycerol kinase from Escherichia ... De Riel, Jon K.; Paulus, Henry (1978). "Subunit dissociation in the allosteric regulation of glycerol kinase from Escherichia ...
... intrinsic dynamics and allosteric regulation". Nat. Struct. Mol. Biol. 26 (7): 545-556. doi:10.1038/s41594-019-0253-7. PMC ... Regulation of NET has been linked to MAPKs, insulin, PKC, and angiotensin II. SERT is responsible for the reuptake of ... Regulation of SERT has been linked to acute depletion of intracellular Ca Na 2+, calmodulin inhibition, CaMKII, Src, p38 MAP ... NET regulation is linked to altered dopamine transmission and schizophrenia-like behaviors. Nisoxetine is a NET inhibitor and ...
Aspartokinases may use the morpheein model of allosteric regulation. In Escherichia coli, aspartokinase is present as three ... This allows the independent regulation of the rates of methionine, lysine, and threonine production. The forms that produce ...
Allosteric regulation Haldane effect Root effect Chloride shift Bohr; Hasselbalch, Krogh. "Concerning a Biologically Important ... The Bohr effect hinges around allosteric interactions between the hemes of the haemoglobin tetramer, a mechanism first proposed ...
RNR1 contains both allosteric sites, mediating regulation of substrate specificity and activity. Depending on the allosteric ... Elledge SJ, Zhou Z, Allen JB (March 1992). "Ribonucleotide reductase: regulation, regulation, regulation". Trends in ... RNR may use the morpheein model of allosteric regulation. Generally Class I RNR inhibitors can be divided in three main groups ... Eliasson R, Pontis E, Jordan A, Reichard P (October 1996). "Allosteric regulation of the third ribonucleotide reductase (NrdEF ...
Goodey, N. M. and Benkovic, S. J. (2008) Allosteric regulation and catalysis emerge via a common route, Nat. Chem. Biol. 4, 474 ... Goodey, Nina M.; Benkovic, Stephen J. (2008-08-01). "Allosteric regulation and catalysis emerge via a common route". Nature ... Pedley, Anthony M.; Benkovic, Stephen J. (2017-02-01). "A New View into the Regulation of Purine Metabolism - The Purinosome". ... allosteric effects are a consequence of creating or inhibiting such networks and drugs can be designed that target such ...
... may use the morpheein model of allosteric regulation. Mast cell tryptase-6 is involved in Trichinella spiralis ...
This protein may use the morpheein model of allosteric regulation. Lipoic acid GRCh38: Ensembl release 89: ENSG00000091140 - ... Wynn RM, Kato M, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT (December 2004). "Molecular mechanism for regulation of the ...
This protein may use the morpheein model of allosteric regulation. Glycerol Kinase (alternative name, ATP:glycerol 3- ...
This protein may use the morpheein model of allosteric regulation. Human CBS performs a crucial step in the biosynthetic ... AdoMet is an allosteric activator that increases the Vmax of the CBS reaction but does not affect the Km for the substrates. In ... Allosteric activation of CBS by adoMet determines the metabolic fate of homocysteine. Mammalian CBS is activated 2.5-5-fold by ... The C-terminal domain of cystathionine β-synthase regulates its activity via both intrasteric and allosteric effects and is ...
This protein may use the morpheein model of allosteric regulation. Hu Y, Komoto J, Huang Y, et al. (June 1999). "Crystal ...
CTP is also subject to various forms of allosteric regulation. GTP acts as an allosteric activator that strongly promotes the ... Since the discovery of this novel mode of enzyme regulation in CTP synthase, multiple other enzymes have been shown to exhibit ... The reaction product CTP also serves as an allosteric inhibitor. The triphosphate binding site overlaps with that of UTP, but ... Endrizzi JA, Kim H, Anderson PM, Baldwin EP (October 2005). "Mechanisms of product feedback regulation and drug resistance in ...
This protein may use the morpheein model of allosteric regulation. Ethanol is dehydrogenated to acetaldehyde by alcohol ... LDH undergoes transcriptional regulation by PGC-1α. PGC-1α regulates LDH by decreasing LDH A mRNA transcription and the ...
This protein may use the morpheein model of allosteric regulation. As of late 2007, two structures have been solved for this ...
This protein may use the morpheein model of allosteric regulation. As of late 2007, two structures have been solved for this ...
This protein may use the morpheein model of allosteric regulation. GRCh38: Ensembl release 89: ENSG00000062485 - Ensembl, May ...
This protein may use the morpheein model of allosteric regulation. PFK is about 300 amino acids in length, and structural ... Sola-Penna M, Da Silva D, Coelho WS, Marinho-Carvalho MM, Zancan P (November 2010). "Regulation of mammalian muscle type 6- ... one involved in ATP binding and the other housing both the substrate-binding site and the allosteric site (a regulatory binding ...
This protein may use the morpheein model of allosteric regulation. Ribonuclease Raines RT (1998). "Ribonuclease A". Chem. Rev. ...
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule ... Ensemble models of allosteric regulation enumerate an allosteric systems statistical ensemble as a function of its potential ... allosteric regulation is also expected to play an increasing role in drug discovery and bioengineering. The AlloSteric Database ... whereas those that decrease the proteins activity are called allosteric inhibitors. Allosteric regulations are a natural ...
... Nat Commun. 2022 Oct 3;13(1):5834. doi: ...
Allosteric regulation of mammalian Na+/I- symporter activity by perchlorate. Download Prime PubMed App to iPhone, iPad, or ... Author Correction: Allosteric Regulation of Mammalian Na+/I- Symporter Activity By Perchlorate. Nat Struct Mol Biol. 2020;27(7 ... Author Correction: Allosteric regulation of mammalian Na+/I- symporter activity by perchlorate. Nat Struct Mol Biol. 2020;27(7 ... Author Correction: Allosteric regulation of mammalian Na+/I- symporter activity by perchlorate.. Nat Struct Mol Biol. 2020 Jul ...
Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the ... To that end, we present a theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model which applies to ...
However, there are no data showing how exactly the regulation emerges from specific lipid-protein interactions. Here we show in ... There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. ... is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β2AR by ...
... signaling plays an important role in the regulation of many cellular functions. Ca2+-binding protein calmodulin (CaM) serves as ... signaling plays an important role in the regulation of many cellular functions. Ca2+-binding protein calmodulin (CaM) serves as ... Ni, D., Lu, S., and Zhang, J. (2019). Emerging roles of allosteric modulators in the regulation of protein-protein interactions ... Mechanistic insights into the role of calcium in the allosteric regulation of the calmodulin-regulated death-associated protein ...
Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease. *Mark ... In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that ... In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that ... the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. ...
Hamill, C. J. (2020). Understanding allosteric enzyme regulation using macromolecular rate theory (Thesis, Master of Science ( ... therefore affecting an enzymes heat capacity and its catalytic rate via ΔCp^‡. Notably, a form of enzyme regulation (called ...
Allosteric regulation controls actin-bundling properties of human plastins *Christopher L. Schwebach ... Our data indicate that Pls3 may act as a break of cell migration and that a tight regulation of its protein levels is critical ... The issues in cell cycle regulation upon homozygous loss of Cul3, however, cannot explain the thinning of cortical layers in ... 9e). Taken together our results indicate that Pls3 is an important player in the fine regulation of cell migration, and its ...
Allosteric drugs bind to sites which are usually less conserved evolutionarily as compared to orthosteric sites. As such, they ... Allosteric Regulation / drug effects * Allosteric Site / drug effects* * Drug Design * Drugs, Investigational / pharmacology* ... From allosteric drugs to allo-network drugs: state of the art and trends of design, synthesis and computational methods Curr ... Allosteric drugs bind to sites which are usually less conserved evolutionarily as compared to orthosteric sites. As such, they ...
Which statement most accurately explains how allosteric regulation can change an enzymes activity? ... Which statement most accurately explains how allosteric regulation can change an enzymes activity? ... c.In allosteric activation a regulatory molecule binds to a site other than the active site, resulting in a change in enzyme ... a. In allosteric deactivation a regulatory molecule binds to a site other than the active site, resulting in a change in enzyme ...
Mechanism and allosteric regulation in ribonucleotide reductases. *Derek Logan. Ribonucleotide reductases (RNRs) are essential ... In addition, they have among the most complex allosteric regulations of any enzyme system. Activity is regulated on two levels ... More recently we have probed the allosteric regulation of class II and class III RNRs by solving the structures of complexes ... as well as of mutants of the T4 RNR which affect the catalytic mechanism and the allosteric regulation. ...
Cancer associated mutations perturb Rad50 D-loop to circumvent allosteric regulation. *Michael Latham (Speaker) ...
Main article: Allosteric regulation. Saturation curve for an enzyme reaction showing sigmoid kinetics.. Many different enzyme ... "Allosteric regulation of catalytic activity: Escherichia coli aspartate transcarbamoylase versus yeast chorismate mutase". ... Allosteric enzymes include mammalian tyrosyl tRNA-synthetase, which shows negative cooperativity,[33] and bacterial aspartate ... Schirmer T, Evans PR (January 1990). "Structural basis of the allosteric behaviour of phosphofructokinase". Nature. 343 (6254 ...
Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1. Nucleic acids research. 2020 Jul 2. doi ... Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1. In: Nucleic acids research. 2020. ... Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1.. Maria Tauber, Sarah Kreuz, Alexander ... Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1. / Tauber, Maria; Kreuz, Sarah; Lemak, ...
Lipid-Mediated Regulation of Embedded Receptor Kinases via Parallel Allosteric Relays. Biophysical journal. 2017 Feb 28;112(4): ... Lipid-Mediated Regulation of Embedded Receptor Kinases via Parallel Allosteric Relays. Madhubrata Ghosh, Loo Chien Wang, Ranita ... Lipid-Mediated Regulation of Embedded Receptor Kinases via Parallel Allosteric Relays. In: Biophysical journal. 2017 ; Vol. 112 ... Lipid-Mediated Regulation of Embedded Receptor Kinases via Parallel Allosteric Relays. / Ghosh, Madhubrata; Wang, Loo Chien; ...
This review will focus on the description of selective and non-selective allosteric modulators of Sig1R, including molecular ... Different experimental approaches have been used to describe and validate the activity of allosteric modulators of Sig1R. Sig1R ... Different experimental approaches have been used to describe and validate the activity of allosteric modulators of Sig1R. Sig1R ... This review will focus on the description of selective and nonselective allosteric modulators of Sig1R, including molecular ...
... ... A. MELLATI, M. YUCEL, N. ALTINORS, and U. Gündüz, "REGULATION OF M2-TYPE PYRUVATE-KINASE FROM HUMAN MENINGIOMA BY ALLOSTERIC ... Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides.. Klinman, DM; Zeuner, R; Yamada, H; Gürsel, ... Regulation and role of CCAAT/enhancer binding protein during differentiation of intestinal epithelial cells. ...
STRUCTURAL BASIS FOR ALLOSTERIC REGULATION AND SUBSTRATE SPECIFICITY OF THE NON-PHOSPHORYLATING GLYCERALDEHYDE-3-PHOSPHATE ... STRUCTURAL BASIS FOR ALLOSTERIC REGULATION AND SUBSTRATE SPECIFICITY OF THE NON-PHOSPHORYLATING GLYCERALDEHYDE-3-PHOSPHATE ... STRUCTURAL BASIS FOR ALLOSTERIC REGULATION AND SUBSTRATE SPECIFICITY OF THE NON-PHOSPHORYLATING GLYCERALDEHYDE-3-PHOSPHATE ...
Structural and dynamic studies provide insights into specificity and allosteric regulation of Ribonuclease AS, a key enzyme in ... Structural and dynamic studies provide insights into specificity and allosteric regulation of Ribonuclease AS, a key enzyme in ... Structural and dynamic studies provide insights into specificity and allosteric regulation of Ribonuclease AS, a key enzyme in ... Structural and dynamic studies provide insights into specificity and allosteric regulation of Ribonuclease AS, a key enzyme in ...
This work establishes a central role for the PIF-pocket on the regulation of PKCζ and allows us to envisage development of ... Notably, we found that the C1 domain allosterically inhibits PKCζ activity and verified an allosteric communication between the ... Allosteric Regulation of Protein Kinase PKCζ by the N-Terminal C1 Domain and Small Compounds to the PIF-Pocket. ... Laura A. Lopez-Garcia, Jörg O. Schulze, Wolfgang Fröhner, Hua Zhang, Evelyn Süss, et al.. Allosteric Regulation of Protein ...
... allosteric regulation. Biochemical and biophysical methods: cell disruption and separation of cell components; protein ...
Kinetic parameters that describe enzyme catalysis, inhibition and allosteric regulation. •Mechanisms of action of several major ...
Allosteric Regulation of the Human Proteasome. Principal Investigator: Michal H. Kolář , Department of Theoretical and ... Recent experimental data revealed that there is an allosteric communication between a core and regulatory parts of the ... In the project, researchers have used atomistic simulations to study molecular details of the allosteric signal - in their ... Understanding the molecular details of these switching events is of great importance to understand cellular regulation and to ...
Research Project: "Structure-function relationship studies of the allosteric regulation in ADP-glucose pyrophosphorylase". ... "Allosteric Regulation Studies of the Bacterial ADP-Glucose Pyrophosphorylase". Mitchell Meves. Billingsley Research Group. ... Research Project: "Molecular Evolution and Reverse Engineering of GabR Regulation Domain, from PLP-binding to Catalysis" ...
Allosteric regulation. Synthesis and degradation of the enzyme. Term. Buffers are said to be most effective within one pH of ... Allosteric modulators seldom resemble the substrate or product of the. enzyme. What does this observation show?. ... bind to allosteric site seperate from active site. sigmodial curve with positive cooperativity. ...
Johnston, J. M. & Bulloch, E. M. Advances in menaquinone biosynthesis: sublocalisation and allosteric regulation. Curr. Opin. ...
... it was an allosteric regulation. In fact, a central station increased the activity of tPA. ... tPA, which was prevalent in the lab, had a cysteine in an allosteric site; cathepsin B, the cysteine was in an active site. So ... that nitric oxide could work through an allosteric mechanism, I then went on, as physician scientists will tend to do, to try ...
Helmstaedt K, Krappmann S, Braus GH (2001) Allosteric regulation of catalytic activity: Escherichia coli aspartate ... Sträter N, Schnappauf G, Braus G, Lipscomb WN (1997) Mechanisms of catalysis and allosteric regulation of yeast chorismate ... Schmidheini T, Mösch HU, Evans JN, Braus G (1990) Yeast allosteric chorismate mutase is locked in the activated state by a ...
  • Allosteric modulators of sigma-1 receptor (Sig1R) are described as compounds that can increase the activity of some Sig1R ligands that compete with (+)-pentazocine, one of the classic prototypical ligands that binds to the orthosteric Sig1R binding site. (frontiersin.org)
  • Different experimental approaches have been used to describe and validate the activity of allosteric modulators of Sig1R. (frontiersin.org)
  • Accumulating evidence suggests that allosteric Sig1R modulators affect processes involved in the pathophysiology of depression, memory and cognition disorders as well as convulsions. (frontiersin.org)
  • This review will focus on the description of selective and non-selective allosteric modulators of Sig1R, including molecular structure properties and pharmacological activity both in vitro and in vivo , with the aim of providing the latest overview from compound discovery approaches to eventual clinical applications. (frontiersin.org)
  • Thus, far no allosteric modulators of Sig2R have been reported. (frontiersin.org)
  • However, the notion that allosteric modulators of Sig1R are identified is an additional argument for the "receptor" view of Sig1R. (frontiersin.org)
  • The binding of allosteric modulators to a target protein induces a conformational change in the protein structure and changes the activity of orthosteric ligands ( Figure 1 ). (frontiersin.org)
  • Allosteric modulators can be positive or negative effectors (PAMs or NAMs, respectively). (frontiersin.org)
  • The definition of allosteric Sig1R modulators might be artificial due to a lack of information on the orthosteric binding site for Sig1R. (frontiersin.org)
  • Thus, allosteric modulators of Sig1R are described as compounds that can increase the activity of Sig1R ligands that compete with [ 3 H](+)-pentazocine for binding to Sig1R. (frontiersin.org)
  • Allosteric modulators seldom resemble the substrate or product of the enzyme. (flashcardmachine.com)
  • We have also analyzed mechanisms by which kinase drugs and allosteric Hsp90 modulators that may act synergistically and exert their pharmacological effect by depriving the client kinase of access to the molecular chaperone. (utoronto.ca)
  • However, direct use of 5-HT 2C receptor positive allosteric modulators in precision medicine is currently being studied. (medscape.com)
  • Ensemble models of allosteric regulation enumerate an allosteric system's statistical ensemble as a function of its potential energy function, and then relate specific statistical measurements of allostery to specific energy terms in the energy function (such as an intermolecular salt bridge between two domains). (wikipedia.org)
  • Integration of computational systems biology and machine learning analysis of the Hsp90 interactions with oncogenic kinase mutants is then used to construct models of allosteric regulation of oncogenic proteins by molecular chaperones in signaling cascades. (utoronto.ca)
  • Allosteric regulation may be facilitated by the evolution of large-scale, low-energy conformational changes, which enables long-range allosteric interaction between distant binding sites. (wikipedia.org)
  • We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. (lu.se)
  • We are also determining the structure of other class III RNRs which have overall activity regulation (the T4 enzyme does not), as well as of mutants of the T4 RNR which affect the catalytic mechanism and the allosteric regulation. (lu.se)
  • Indeed, they provide a possible mechanism of allosteric regulation, which unlocks one catalytic groove when the second groove is inhibited by the double strand region of tRNA. (cnr.it)
  • Allosteric conversion of partial to full agonism may be a general mechanism for reversibly scaling the efficacy of GABA A receptors to endogenous partial agonists. (jneurosci.org)
  • Network-defined modularity of interacting components and cross-talk in signal transduction networks are quantified through molecular mechanism of allosteric regulation. (utoronto.ca)
  • This type of negative regulation by ATP is by an allosteric mechanism. (citizendium.org)
  • This mechanism for regulation is due to substrate inhibition by NADH of the enzymes that use NAD+ as a substrate. (citizendium.org)
  • Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are called allosteric inhibitors. (wikipedia.org)
  • In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. (lu.se)
  • This relatively unexplored therapeutic potential and the putative advantages of allosteric drugs over classical active-site inhibitors fuel the attention allosteric-drug research is receiving at present. (biomedcentral.com)
  • An important factor fueling interest in allosteric drugs consists in their characteristic advantages compared to traditional active-site inhibitors. (biomedcentral.com)
  • LCFA-CoA esters promote their own oxidation by acting as allosteric inhibitors of acetyl-CoA carboxylase, which reduces the production of malonyl-CoA and relieves inhibition of carnitine palmitoyl-transferase 1, thereby promoting LCFA-CoA transport into the mitochondria for β-oxidation2-6. (mcmaster.ca)
  • In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. (wikipedia.org)
  • Allosteric regulation is also particularly important in the cell's ability to adjust enzyme activity. (wikipedia.org)
  • Notably, a form of enzyme regulation (called allostery) utilises ligand binding at a site other than the active site to effect changes in catalytic rate. (waikato.ac.nz)
  • In allosteric deactivation a regulatory molecule binds to a site other than the active site, resulting in a change in enzyme shape that allows the active site to bind substrate. (nursingdons.com)
  • In addition, they have among the most complex allosteric regulations of any enzyme system. (lu.se)
  • Understanding Abl's regulation is important because a mutant form of the enzyme (Bcr-Abl) is over activated in chronic myelogenous leukemia and other cancers. (stjude.org)
  • The Abl enzyme controls this switching through a process called allosteric regulation in which a part of the molecule distant from the molecule's on-off switch or kinase domain somehow inhibits or activates Abl. (stjude.org)
  • The different conformations of Arg80 coupled to rearrangements in the quaternary structure imply that this residue plays a major role in regulation of the enzyme and in communication between subunits. (rcsb.org)
  • To summarize: subunits need not exist in the same conformation molecules of substrate bind via induced-fit protocol conformational changes are not propagated to all subunits The morpheein model of allosteric regulation is a dissociative concerted model. (wikipedia.org)
  • In allosteric activation a regulatory molecule binds to the active site, allowing substrate binding. (nursingdons.com)
  • More recently we have probed the allosteric regulation of class II and class III RNRs by solving the structures of complexes with several combinations of allosteric effector and substrate [2,5]. (lu.se)
  • Number of selective Sig1R and Sig2R ligands have been described confirming significant differences in the pharmacological regulation of these subtypes. (frontiersin.org)
  • In this article, we describe a simple computational approach, based on the effect allosteric ligands exert on protein flexibility upon binding, to predict the existence and position of allosteric sites on a given protein structure. (biomedcentral.com)
  • We also analyzed four biological examples in detail, revealing that this simple coarse-grained methodology is able to capture the effects triggered by allosteric ligands already described in the literature. (biomedcentral.com)
  • Allosteric regulation of PKCθ: understanding multistep phosphorylation and priming by ligands in AGC kinases. (ub.edu)
  • The site to which the effector binds is termed the allosteric site or regulatory site. (wikipedia.org)
  • This is in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site. (wikipedia.org)
  • To that end, we present a theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model which applies to a variety of regulatory architectures. (aps.org)
  • A first step to harness the regulatory potential and versatility of allosteric sites, in the context of drug-discovery and design, would be to detect or predict their presence and location. (biomedcentral.com)
  • Allosteric interactions of the Hsp90 with cochaperones and protein kinase clients can determine regulatory mechanisms and cellular functions of many signaling proteins and cascades. (utoronto.ca)
  • Biophysical modeling of allosteric regulation in the protein kinases has offered additional insights into organizing principles of kinase activation by molecular chaperones that may be orchestrated by a cross-talk between key regulatory regions. (utoronto.ca)
  • The researchers' experiments explored in detail how the region of Abl called the allosteric regulatory module interacted with the kinase domain to control it. (stjude.org)
  • Allosteric modulation is used to alter the activity of molecules and enzymes in biochemistry and pharmacology. (wikipedia.org)
  • It is even more intriguing to consider the potential plasticity of allosteric modulation given the observation of agonist-dependent functional properties of GABA A receptors. (jneurosci.org)
  • However, for most allosteric proteins identified to date the mechanistic details of allosteric modulation are not yet well understood. (biomedcentral.com)
  • β1 subunit mutations that inhibit AMPK activation by the small-molecule activator A769662, which binds to the allosteric drug and metabolite site, also inhibit activation by LCFA-CoAs. (mcmaster.ca)
  • Our results highlight the importance of flexible linkers in regulating multidomain chromatin binding proteins and point to divergent evolution of their regulation. (edu.sa)
  • By querying the literature and a recently available database of allosteric sites, we gathered 213 allosteric proteins with structural information that we further filtered into a non-redundant set of 91 proteins. (biomedcentral.com)
  • Its performance has been demonstrated using a newly curated non-redundant set of 91 proteins with reported allosteric properties. (biomedcentral.com)
  • Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change and/or a change in protein dynamics. (wikipedia.org)
  • Allosteric drugs bind to sites which are usually less conserved evolutionarily as compared to orthosteric sites. (nih.gov)
  • There is now a new generation of drugs that bind to the allosteric pocket to inhibit its activity,' he said. (stjude.org)
  • While many of the mutations block Gleevec from plugging into the kinase domain, others appear to interfere with the allosteric regulation. (stjude.org)
  • These could be combined with Gleevec to overcome allosteric mutations to shift Abl into an inhibited state. (stjude.org)
  • The results of biophysical and computational systems biology analyses combined with proteomics experiments have been integrated into a graph-based network model of allosteric regulation. (utoronto.ca)
  • The allostery landscape model introduced by Cuendet, Weinstein, and LeVine allows for the domains to have any number of states and the contribution of a specific molecular interaction to a given allosteric coupling can be estimated using a rigorous set of rules. (wikipedia.org)
  • Allostery is one of the most powerful and common ways of regulation of protein activity. (biomedcentral.com)
  • Tight regulation of these processes is fundamental in all kingdoms of life and allostery represents one of the most commmon and powerful means of modulating protein activity[ 1 ]. (biomedcentral.com)
  • Allostery can be defined as the regulation of a protein's function by binding of an effector molecule at a site which is not the active site. (biomedcentral.com)
  • These results agree with the current view that allosteric mechanisms are in many cases governed by changes in protein dynamics caused by ligand binding. (biomedcentral.com)
  • At present, allosteric phenomena are being intensively studied for their potential as target mechanisms for the development of new classes of therapeutics[ 4 ]. (biomedcentral.com)
  • Here we show in atomistic detail how the human β2-adrenergic receptor (β2AR) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. (helsinki.fi)
  • GLP-1 is a physiologic regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. (medscape.com)
  • The allosteric interactions and regulation of molecular chaperones and protein kinases allow for molecular communication and event coupling in signal transduction networks. (utoronto.ca)
  • Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of. (lu.se)
  • We performed normal-mode analysis and observed significant changes in protein flexibility upon allosteric-ligand binding in 70% of the cases. (biomedcentral.com)
  • We introduce a simple computational approach to predict the presence and position of allosteric sites in a protein based on the analysis of changes in protein normal modes upon the binding of a coarse-grained ligand at predicted cavities. (biomedcentral.com)
  • Activation of AMPK by LCFA-CoA esters requires the allosteric drug and metabolite site formed between the α-subunit kinase domain and the β-subunit. (mcmaster.ca)
  • This mini-hot-topic issue of CTMC showcases some successes and challenges of allosteric drug development through the examples of seventransmembrane (GPCR), AMPA, NMDA and metabotropic glutamate receptors, as well as the morpheein model of allosterism involved in inherent metabolic errors. (nih.gov)
  • There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. (helsinki.fi)
  • These components are integrated through long-range communication relays, with lipids playing an essential role in regulation. (utmb.edu)
  • Allosteric regulation is the regulation of protein activity by binding an effector molecule at a site other than the orthosteric or active site of a protein ( Figure 1 ). (frontiersin.org)
  • As bioactive molecule, ceramide is involved in the regulation of many cellular processes. (elifesciences.org)
  • Such regulation would involve pushing the Abl molecule toward either the inhibited or activated shape, he said. (stjude.org)
  • Finally, the development of allo-network drugs, which are allosteric drugs acting indirectly on the neighborhood of the pharmacological target in protein-protein interaction or signaling networks, is described. (nih.gov)
  • Which statement most accurately explains how allosteric regulation can change an enzyme's activity? (nursingdons.com)
  • Notably, we found that the C1 domain allosterically inhibits PKCζ activity and verified an allosteric communication between the PIF-pocket of atypical PKCs and the binding site of the C1 domain. (hal.science)
  • Furthermore, we implemented an approach that achieves 65% positive predictive value in identifying allosteric sites within the set of predicted cavities of a protein (stricter parameters set, 0.22 sensitivity), by combining the current analysis on dynamics with previous results on structural conservation of allosteric sites. (biomedcentral.com)
  • Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides. (metu.edu.tr)
  • Ultrasensitive regulation of anapleurosis via allosteric activation of PEP carboxylase. (princeton.edu)
  • Here we report a new level of regulation wherein LCFA-CoA esters per se allosterically activate AMP-activated protein kinase (AMPK) β1-containing isoforms to increase fatty acid oxidation through phosphorylation of acetyl-CoA carboxylase. (mcmaster.ca)
  • This work establishes a central role for the PIF-pocket on the regulation of PKCζ and allows us to envisage development of drugs targeting the PIF-pocket that can either activate or inhibit AGC kinases. (hal.science)
  • For example, allosteric sites tend to be under lower sequence-conservation pressure than active sites, facilitating the design of highly specific drugs and reducing the risks of toxicity or side-effects[ 5 - 7 ]. (biomedcentral.com)
  • To understand the allosteric regulation, crystal structures were determined for S. solfataricus UPRTase in complex with UMP and with UMP and the allosteric inhibitor CTP. (rcsb.org)
  • Many allosteric effects can be explained by the concerted MWC model put forth by Monod, Wyman, and Changeux, or by the sequential model (also known as the KNF model) described by Koshland, Nemethy, and Filmer. (wikipedia.org)
  • This regulation ensures that the TCA cycle will not oxidise excessive amounts of pyruvate and acetyl-CoA when ATP in the cell is plentiful. (citizendium.org)
  • Calcium (Ca 2+ ) signaling plays an important role in the regulation of many cellular functions. (frontiersin.org)
  • Ensemble models like the ensemble allosteric model and allosteric Ising model assume that each domain of the system can adopt two states similar to the MWC model. (wikipedia.org)
  • Allosteric regulations are a natural example of control loops, such as feedback from downstream products or feedforward from upstream substrates. (wikipedia.org)