Nucleoside-Diphosphate Kinase
NM23 Nucleoside Diphosphate Kinases
Nucleoside Diphosphate Kinase D
Monomeric GTP-Binding Proteins
Nucleosides
Guanosine Diphosphate
Phosphotransferases
Guanosine Triphosphate
Halomonas
Molecular Sequence Data
Succinate-CoA Ligases
Adenosine Triphosphate
Nucleotides
Amino Acid Sequence
Dictyostelium
Phosphorylation
Guanosine Monophosphate
Escherichia coli
Adenosine Diphosphate
Nucleoside Diphosphate Sugars
Pyruvate Kinase
Adenylate Kinase
Enzyme Stability
Peas
Catalysis
Substrate Specificity
Cytidine Diphosphate
5'-Nucleotidase
Sequence Homology, Amino Acid
Base Sequence
Isoenzymes
GTP-Binding Proteins
Cloning, Molecular
Pyrimidine Nucleosides
Serine
Nucleoside Transport Proteins
Models, Molecular
Chromatography, Gel
Mutation
Crystallization
Electrophoresis, Polyacrylamide Gel
DNA Primers
Protein Conformation
Protein Binding
Transcription Factors
Mutagenesis, Site-Directed
Phosphatidylinositol 3-Kinases
Electrophoresis, Gel, Two-Dimensional
Cell Membrane
Crystallography, X-Ray
MAP Kinase Signaling System
Binding Sites
Protein Kinases
Protein-Serine-Threonine Kinases
Pseudomonas aeruginosa
Equilibrative Nucleoside Transporter 1
Uridine Diphosphate
Structure-Activity Relationship
Blotting, Western
Alkyl and Aryl Transferases
Dose-Response Relationship, Drug
Cattle
Cyclic AMP
Mitochondria
Pyrophosphatases
Inhibition of nucleoside diphosphate kinase in rat liver mitochondria by added 3'-azido-3'-deoxythymidine. (1/491)
The effect of 3'-azido-3'-deoxythymidine on nucleoside diphosphate kinase of isolated rat liver mitochondria has been studied. This is done by monitoring the increase in the rate of oxygen uptake by nucleoside diphosphate (TDP, UDP, CDP or GDP) addition to mitochondria in state 4. It is shown that 3'-azido-3'-deoxythymidine inhibits the mitochondrial nucleoside diphosphate kinase in a competitive manner, with a Ki value of about 10 microM as measured for each tested nucleoside diphosphate. It is also shown that high concentrations of GDP prevent 3'-azido-3'-deoxythymidine inhibition of the nucleoside diphosphate kinase. (+info)Overexpression of nucleoside diphosphate kinases induces neurite outgrowth and their substitution to inactive forms leads to suppression of nerve growth factor- and dibutyryl cyclic AMP-induced effects in PC12D cells. (2/491)
Whether nucleoside diphosphate kinase (NDPK) is involved in neuronal differentiation was investigated with special reference to its enzyme activity. Neurite outgrowth of PC12D cells induced by nerve growth factor or a cyclic AMP analog was suppressed to some extent when inactive NDPKs (the active site histidine 118 was replaced with alanine), not active forms, were transiently overexpressed. This suppression was more definite in their stably expressed clones. NDPKbeta-transfected clones and, to a lesser extent, NDPKalpha-transfected clones, but not inactive NDPK-transfected clones, extended neurites without differentiation inducers. These results imply that NDPKs may play a role by exerting their enzyme activity during differentiation of PC12 cells. (+info)Selecting near-native conformations in homology modeling: the role of molecular mechanics and solvation terms. (3/491)
A free energy function, combining molecular mechanics energy with empirical solvation and entropic terms, is used for ranking near-native conformations that occur in the conformational search steps of homology modeling, i.e., side-chain search and loop closure calculations. Correlations between the free energy and RMS deviation from the X-ray structure are established. It is shown that generally both molecular mechanics and solvation/entropic terms should be included in the potential. The identification of near-native backbone conformations is accomplished primarily by the molecular mechanics term that becomes the dominant contribution to the free energy if the backbone is even slightly strained, as frequently occurs in loop closure calculations. Both terms become equally important if a sufficiently accurate backbone conformation is found. Finally, the selection of the best side-chain positions for a fixed backbone is almost completely governed by the solvation term. The discriminatory power of the combined potential is demonstrated by evaluating the free energies of protein models submitted to the first meeting on Critical Assessment of techniques for protein Structure Prediction (CASP1), and comparing them to the free energies of the native conformations. (+info)Nucleoside diphosphate kinase activity in soluble transducin preparations biochemical properties and possible role of transducin-beta as phosphorylated enzyme intermediate. (4/491)
Known nucleoside diphosphate kinases (NDPKs) are oligomers of 17-23-kDa subunits and catalyze the reaction N1TP + N2DP --> N1DP + N2TP via formation of a histidine-phosphorylated enzyme intermediate. NDPKs are involved in the activation of heterotrimeric GTP-binding proteins (G-proteins) by catalyzing the formation of GTP from GDP, but the properties of G-protein-associated NDPKs are still incompletely known. The aim of our present study was to characterize NDPK in soluble preparations of the retinal G-protein transducin. The NDPK is operationally referred to as transducin-NDPK. Like known NDPKs, transducin-NDPK utilizes NTPs and phosphorothioate analogs of NTPs as substrates. GDP was a more effective phosphoryl group acceptor at transducin-NDPK than ADP and CDP, and guanosine 5'-[gamma-thio]triphosphate (GTP[S]) was a more effective thiophosphoryl group donor than adenosine 5'-[gamma-thio]triphosphate (ATP[S]). In contrast with their action on known NDPKs, mastoparan and mastoparan 7 had no stimulatory effect on transducin-NDPK. Guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) potentiated [3H]GTP[S] formation from [3H]GDP and ATP[S] but not [3H]GTP[S] formation from [3H]GDP and GTP[S]. Depending on the thiophosphoryl group acceptor and donor, [3H]NTP[S] formation was differentially regulated by Mg2+, Mn2+, Co2+, Ca2+ and Zn2+. [gamma-32P]ATP and [gamma-32P]GTP [32P]phosphorylated, and [35S]ATP[S] [35S]thiophosphorylated, a 36-kDa protein comigrating with transducin-beta. p[NH]ppG potentiated [35S]thiophosphorylation of the 36-kDa protein. 32P-labeling of the 36-kDa protein showed characteristics of histidine phosphorylation. There was no evidence for (thio)phosphorylation of 17-23-kDa proteins. Our data show the following: (a) soluble transducin preparations contain a GDP-prefering and guanine nucleotide-regulated NDPK; (b) transducin-beta may serve as a (thio)phosphorylated NDPK intermediate; (c) transducin-NDPK is distinct from known NDPKs and may consist of multiple kinases or a single kinase with multiple regulatory domains. (+info)Study on the metastatic mechanisms of human giant-cell lung carcinoma comparison between the strains C and D. (5/491)
The biologic characteristics of the two human giant-cell lung carcinoma strains with high (strain D) and low metastatic potential (strain C) were studied, including karyotype of chromosome, intracellular free calcium ([Ca2+]i), morphologic changes of cell surface and the expression of nm23-H1, p53, ras, c-myc, c-erbB2, bcl-2 genes and PCNA. The correlation between different biologic features and the metastatic potential of the two strains was analyzed. We found: 1) Both strains had the karyotypic abnormality of -13, -14, -15, +20, +21 with seven same marker chromosomes. Only strain D had the karyotypic abnormality of +7, -17, -18, +X, 7p+; 2) [Ca2+]i of the strain C (984.7 +/- 573.8) and D (517.6 +/- 216.6) was significantly different (p < 0.05). The amplitude of intracellular calcium oscillations of strain C was lower than the one of strain D; 3) strain C had more villous-like protrusions on the cell surface, whereas strain D had more bubble-like protrusions; 4) The expression of nm23-H1 and p53 protein of strain C was all higher than that of strain D. The expression of PCNA of strain C was lower than strain D; 5) nm23-H1 mRNA levels of strain C was lower than that of strain D. We consider that the karyotype of chromosomes, intracellular free calcium, the structure of cell membrane and the expression of nm23-H1 gene, p53 gene, PCNA could be closely related to the metastatic potential of human giant-cell lung carcinoma. They could be used as the sign for judging whether the tumor will metastasize in clinical practice as well as in judging the prognoses of patients. (+info)Isolation of cDNA clones encoding two isoforms of nucleoside diphosphate kinase from bovine retina. (6/491)
The cDNA encoding bovine retinal isoforms of nucleoside diphosphate kinase (NDP-kinase, EC 2.7.4.6) has been cloned and sequenced. Based on the partial amino acid sequence of the enzyme determined after trypsin digestion of purified NDP-kinase, primers were synthesized and used to isolate two different cDNA clones encoding the full length of two NDP-kinase isoforms. The nucleotide sequences of these clones contained open reading frames encoding 152-residue polypeptides with calculated molecular masses of 17.262 and 17.299 kDa, similar to that determined for the subunits of purified enzyme (17.5 and 18.5 kDa). The deduced NDP-kinase sequences showed high similarity with the known NDP-kinase sequences from other sources. (+info)Frequent allelic losses at 11q24.1-q25 in young women with breast cancer: association with poor survival. (7/491)
Previous studies have demonstrated that the pathological features of breast cancer are more aggressive in younger women than in their older counterparts, and that young age may be an independent marker for adverse prognosis. These findings have raised the question whether these differences are also present at the molecular level. In order to characterize the genetic alterations associated with early-onset breast cancer, 102 cases selected for age under 37 at diagnosis were examined for loss of heterozygosity (LOH) at nine different loci on chromosomes 11, 13 and 17. Ninety cases (88%), exhibited LOH for at least one marker. The D17S855 marker, intragenic in the BRCA1 gene, showed a high proportion of LOH (63%), whereas the intragenic marker for the TP53 gene, HP53, exhibited LOH in 43% of the cases. On chromosome 11, frequencies of LOH peaked at the D11S969 and D11S387 markers, which expressed LOH in 53% and 48% of the informative cases, whereas D11S1818, which is proximate to the ATM gene, exhibited an LOH frequency of 24%. A statistically significant correlation was found between LOH at the D11S387 marker and poor survival (P = 0.028). No such correlation was found for the adjacent D11S969 marker, located approximately 500 kb centromeric to D11S387. We conclude that one or more as yet unidentified genes, situated in chromosome bands 11q24.1-q25, could be involved in the initiation and/or progression of breast cancer in younger women. (+info)Alterations of oncogenes, tumor suppressor genes and growth factors in hepatocellular carcinoma: with relation to tumor size and invasiveness. (8/491)
OBJECTIVE: To make a better understanding of the molecular mechanisms involved in recurrence and metastasis of the hepatocellular carcinoma (HCC), some invasion related oncogenes, and growth factors have been investigated. METHODS: The studies were separately carried out, the results of which were summarized in this article with relation to tumor size and invasiveness of HCC. RESULTS: The aberration rates of p53 and CDKN2 in HCC were 45.9% and 36.4% respectively, which were higher in invasive HCC compared with non-invasive HCC. H-ras expression was positive in 29.3% of HCC, which was associated with recurrence and extrahepatic metastasis of HCC. Intralesional injection of H-ras antisense gene markedly inhibited the tumor growth and metastasis of HCC in nude mice. The positive rates of transforming growth factor (TGF)-alpha, epidermal growth factor receptor (EGFR) and c-erbB-2 were 45.7%, 47.1% and 92.3% respectively. The expression of EGFR was closely related to TGF-alpha, which was related to HCC recurrence. But no obvious difference of TGF-alpha or c-erbB-2 expression was found between HCC with and without recurrence, or with and without extrahepatic metastasis. Expression of nm23/tissue inhibitor of metalloproteinase (TIMP)-2 was positively associated with the prognosis of HCC patients (Log-rank, P < 0.001). The alterative rates of above-mentioned genes and growth factors in small HCC were slightly lower than that in large ones, but no significant difference was shown except the p53 mutation. CONCLUSIONS: The p53/CDKN2 mutation, over-expression of H-ras/EGFR, were associated with the invasiveness and recurrence of HCC. H-ras antisense gene might be of potential implication in the control of HCC recurrence and metastasis. Expression of nm23/TIMP-2 was closely related to the prognosis of HCC patients. Biological characteristics remained critical points to the prognosis even in small HCC. (+info)Nucleoside-diphosphate kinase (NDK) is an enzyme that plays a crucial role in the regulation of intracellular levels of nucleoside triphosphates and diphosphates. These nucleotides are essential for various cellular processes, including DNA replication, transcription, translation, and energy metabolism.
NDK catalyzes the transfer of a phosphate group from a nucleoside triphosphate (most commonly ATP or GTP) to a nucleoside diphosphate (NDP), converting it into a nucleoside triphosphate (NTP). The reaction can be summarized as follows:
NTP + NDP ↔ NDP + NTP
The enzyme has several isoforms, which are differentially expressed in various tissues and cellular compartments. In humans, there are nine known isoforms of NDK, classified into three subfamilies: NM23-H (NME1), NM23-H2 (NME2), and NME4-8. These isoforms share a conserved catalytic core but differ in their regulatory domains and cellular localization.
NDK has been implicated in several physiological processes, such as cell proliferation, differentiation, and survival. Dysregulation of NDK activity has been associated with various pathological conditions, including cancer, neurodegenerative diseases, and viral infections.
NM23 nucleoside diphosphate kinases are a group of proteins that play a role in regulating cellular functions, including signal transduction, cell proliferation, and differentiation. They are named after the NM23 gene that encodes them, which was initially identified as a potential metastasis suppressor.
NM23 nucleoside diphosphate kinases have the ability to transfer phosphate groups between nucleoside diphosphates (NDPs) and nucleoside triphosphates (NTPs), thereby maintaining the balance of these molecules in cells. This enzymatic activity is important for various cellular processes, such as DNA replication, repair, and transcription.
There are several isoforms of NM23 nucleoside diphosphate kinases, including NM23-H1, NM23-H2, and NM23-H4, which differ in their tissue distribution and functions. While the role of NM23 as a metastasis suppressor has been debated, recent studies suggest that it may be involved in regulating cell motility and invasion through its effects on actin dynamics and microtubule organization.
Overall, NM23 nucleoside diphosphate kinases are important regulators of cellular homeostasis and have been implicated in various physiological and pathological processes, including cancer metastasis, inflammation, and neurodegenerative diseases.
Nucleoside diphosphate kinase D (NDKD), also known as NM23-H4, is an enzyme that belongs to the nucleoside diphosphate kinase family. This family of enzymes plays a crucial role in cellular energy metabolism by catalyzing the transfer of phosphate groups between different nucleotides. Specifically, NDKD catalyzes the conversion of nucleoside diphosphates (NDPs) to nucleoside triphosphates (NTPs) and vice versa, using another NTP as a phosphate donor.
NDKD is primarily located in the mitochondria and has been found to be involved in various cellular processes, including DNA replication, repair, and transcription, as well as cell signaling and differentiation. Mutations in the gene encoding NDKD have been associated with certain types of cancer, such as neuroblastoma and hepatocellular carcinoma, suggesting that this enzyme may play a role in tumor suppression or progression. However, further research is needed to fully understand the functional significance of NDKD in these contexts.
Monomeric GTP-binding proteins, also known as small GTPases, are a family of proteins that bind and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). These proteins function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. They play crucial roles in regulating various cellular processes such as signal transduction, vesicle trafficking, cytoskeleton organization, and cell cycle progression. Examples of monomeric GTP-binding proteins include Ras, Rho, Rab, and Ran families.
A nucleoside is a biochemical molecule that consists of a pentose sugar (a type of simple sugar with five carbon atoms) covalently linked to a nitrogenous base. The nitrogenous base can be one of several types, including adenine, guanine, cytosine, thymine, or uracil. Nucleosides are important components of nucleic acids, such as DNA and RNA, which are the genetic materials found in cells. They play a crucial role in various biological processes, including cell division, protein synthesis, and gene expression.
Guanosine diphosphate (GDP) is a nucleotide that consists of a guanine base, a sugar molecule called ribose, and two phosphate groups. It is an ester of pyrophosphoric acid with the hydroxy group of the ribose sugar at the 5' position. GDP plays a crucial role as a secondary messenger in intracellular signaling pathways and also serves as an important intermediate in the synthesis of various biomolecules, such as proteins and polysaccharides.
In cells, GDP is formed from the hydrolysis of guanosine triphosphate (GTP) by enzymes called GTPases, which convert GTP to GDP and release energy that can be used to power various cellular processes. The conversion of GDP back to GTP can be facilitated by nucleotide diphosphate kinases, allowing for the recycling of these nucleotides within the cell.
It is important to note that while guanosine diphosphate has a significant role in biochemical processes, it is not typically associated with medical conditions or diseases directly. However, understanding its function and regulation can provide valuable insights into various physiological and pathophysiological mechanisms.
Phosphotransferases are a group of enzymes that catalyze the transfer of a phosphate group from a donor molecule to an acceptor molecule. This reaction is essential for various cellular processes, including energy metabolism, signal transduction, and biosynthesis.
The systematic name for this group of enzymes is phosphotransferase, which is derived from the general reaction they catalyze: D-donor + A-acceptor = D-donor minus phosphate + A-phosphate. The donor molecule can be a variety of compounds, such as ATP or a phosphorylated protein, while the acceptor molecule is typically a compound that becomes phosphorylated during the reaction.
Phosphotransferases are classified into several subgroups based on the type of donor and acceptor molecules they act upon. For example, kinases are a subgroup of phosphotransferases that transfer a phosphate group from ATP to a protein or other organic compound. Phosphatases, another subgroup, remove phosphate groups from molecules by transferring them to water.
Overall, phosphotransferases play a critical role in regulating many cellular functions and are important targets for drug development in various diseases, including cancer and neurological disorders.
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.
"Halomonas" is a genus of bacteria that are found in saline environments, such as salt lakes, marine habitats, and salted food products. These bacteria are characterized by their ability to grow optimally in media with high salt concentrations (up to 20-30% sodium chloride). They are generally rod-shaped and motile, with a gram-negative cell wall structure. Some species of Halomonas have been studied for their potential applications in biotechnology, such as the production of compatible solutes, enzymes, and biofuels. However, it is important to note that "Halomonas" is not a medical term per se, but rather a taxonomic designation used in microbiology and related fields.
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.
According to the US National Library of Medicine's Medical Subject Headings (MeSH), Succinate-CoA Ligases are defined as:
Enzymes that catalyze the conversion of succinyl-CoA and diphosphate into CoA, carbon dioxide, and a high-energy phosphate bond in an ATP or a GTP molecule. They are classified into two types according to the type of high-energy phosphate bond they form: adenosine triphosphatases (succinate-coa ligase (adenosine triphosphate)) or guanosine triphosphatases (succinate-coa ligase (guanosine triphosphate)).
Source: National Library of Medicine. (2021). Succinate-CoA Ligases. In: MeSH Database. Bethesda, MD: National Library of Medicine. Available at:
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.
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 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.
'Dictyostelium' is a genus of social amoebae that are commonly found in soil and decaying organic matter. These microscopic organisms have a unique life cycle, starting as individual cells that feed on bacteria. When food becomes scarce, the cells undergo a developmental process where they aggregate together to form a multicellular slug-like structure called a pseudoplasmodium or grex. This grex then moves and differentiates into a fruiting body that can release spores for further reproduction.
Dictyostelium discoideum is the most well-studied species in this genus, serving as a valuable model organism for research in various fields such as cell biology, developmental biology, and evolutionary biology. The study of Dictyostelium has contributed significantly to our understanding of fundamental biological processes like chemotaxis, signal transduction, and cell differentiation.
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.
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.
Guanosine monophosphate (GMP) is a nucleotide that is a fundamental unit of genetic material in DNA and RNA. It consists of a guanine base, a pentose sugar (ribose in the case of RNA, deoxyribose in DNA), and one phosphate group. GMP plays crucial roles in various biochemical reactions within cells, including energy transfer and signal transduction pathways. Additionally, it is involved in the synthesis of important molecules like nucleic acids, neurotransmitters, and hormones.
'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.
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.
Nucleoside diphosphate sugars (NDP-sugars) are essential activated sugars that play a crucial role in the biosynthesis of complex carbohydrates, such as glycoproteins and glycolipids. They consist of a sugar molecule linked to a nucleoside diphosphate, which is formed from a nucleotide by removal of one phosphate group.
NDP-sugars are created through the action of enzymes called nucleoside diphosphate sugars synthases or transferases, which transfer a sugar molecule from a donor to a nucleoside diphosphate, forming an NDP-sugar. The resulting NDP-sugar can then be used as a substrate for various glycosyltransferases that catalyze the addition of sugars to other molecules, such as proteins or lipids.
NDP-sugars are involved in many important biological processes, including cell signaling, protein targeting, and immune response. They also play a critical role in maintaining the structural integrity of cells and tissues.
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.
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.
Adenylate kinase is an enzyme (EC 2.7.4.3) that catalyzes the reversible transfer of a phosphate group between adenine nucleotides, specifically between ATP and AMP to form two ADP molecules. This reaction plays a crucial role in maintaining the energy charge of the cell by interconverting these important energy currency molecules.
The general reaction catalyzed by adenylate kinase is:
AMP + ATP ↔ 2ADP
This enzyme is widely distributed in various organisms and tissues, including mammalian cells. In humans, there are several isoforms of adenylate kinase, located in different cellular compartments such as the cytosol, mitochondria, and nucleus. These isoforms have distinct roles in maintaining energy homeostasis and protecting cells under stress conditions. Dysregulation of adenylate kinase activity has been implicated in several pathological processes, including neurodegenerative diseases, ischemia-reperfusion injury, and cancer.
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.
I'm sorry for any confusion, but "peas" is not a term typically used in medical definitions. Peas are a type of legume that is commonly consumed as a vegetable. They are rich in nutrients such as protein, fiber, vitamin C, and vitamin K. If you have any questions about the health benefits or potential risks of consuming peas, I would be happy to try to help with that.
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.
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.
Purine nucleosides are fundamental components of nucleic acids, which are the genetic materials found in all living organisms. A purine nucleoside is composed of a purine base (either adenine or guanine) linked to a sugar molecule, specifically ribose in the case of purine nucleosides.
The purine base and sugar moiety are joined together through a glycosidic bond at the 1' position of the sugar. These nucleosides play crucial roles in various biological processes, including energy transfer, signal transduction, and as precursors for the biosynthesis of DNA and RNA.
In the human body, purine nucleosides can be derived from the breakdown of endogenous nucleic acids or through the dietary intake of nucleoproteins. They are further metabolized to form uric acid, which is eventually excreted in the urine. Elevated levels of uric acid in the body can lead to the formation of uric acid crystals and contribute to the development of gout or kidney stones.
Cytidine diphosphate (CDP) is a nucleotide that is a constituent of coenzymes and plays a role in the synthesis of lipids, such as phosphatidylcholine and sphingomyelin, which are important components of cell membranes. It is formed from cytidine monophosphate (CMP) through the addition of a second phosphate group by the enzyme CTP synthase. CDP can also be converted to other nucleotides, such as uridine diphosphate (UDP) and deoxythymidine diphosphate (dTDP), through the action of various enzymes. These nucleotides play important roles in the biosynthesis of carbohydrates, lipids, and other molecules in the cell.
5'-Nucleotidase is an enzyme that is found on the outer surface of cell membranes, including those of liver cells and red blood cells. Its primary function is to catalyze the hydrolysis of nucleoside monophosphates, such as adenosine monophosphate (AMP) and guanosine monophosphate (GMP), to their corresponding nucleosides, such as adenosine and guanosine, by removing a phosphate group from the 5' position of the nucleotide.
Abnormal levels of 5'-Nucleotidase in the blood can be indicative of liver or bone disease. For example, elevated levels of this enzyme in the blood may suggest liver damage or injury, such as that caused by hepatitis, cirrhosis, or alcohol abuse. Conversely, low levels of 5'-Nucleotidase may be associated with certain types of anemia, including aplastic anemia and paroxysmal nocturnal hemoglobinuria.
Medical professionals may order a 5'-Nucleotidase test to help diagnose or monitor the progression of these conditions. It is important to note that other factors, such as medication use or muscle damage, can also affect 5'-Nucleotidase levels, so results must be interpreted in conjunction with other clinical findings and diagnostic tests.
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.
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.
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.
Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.
Molecular weight, also known as molecular mass, is the mass of a molecule. It is expressed in units of atomic mass units (amu) or daltons (Da). Molecular weight is calculated by adding up the atomic weights of each atom in a molecule. It is a useful property in chemistry and biology, as it can be used to determine the concentration of a substance in a solution, or to calculate the amount of a substance that will react with another in a chemical reaction.
GTP-binding proteins, also known as G proteins, are a family of molecular switches present in many organisms, including humans. They play a crucial role in signal transduction pathways, particularly those involved in cellular responses to external stimuli such as hormones, neurotransmitters, and sensory signals like light and odorants.
G proteins are composed of three subunits: α, β, and γ. The α-subunit binds GTP (guanosine triphosphate) and acts as the active component of the complex. When a G protein-coupled receptor (GPCR) is activated by an external signal, it triggers a conformational change in the associated G protein, allowing the α-subunit to exchange GDP (guanosine diphosphate) for GTP. This activation leads to dissociation of the G protein complex into the GTP-bound α-subunit and the βγ-subunit pair. Both the α-GTP and βγ subunits can then interact with downstream effectors, such as enzymes or ion channels, to propagate and amplify the signal within the cell.
The intrinsic GTPase activity of the α-subunit eventually hydrolyzes the bound GTP to GDP, which leads to re-association of the α and βγ subunits and termination of the signal. This cycle of activation and inactivation makes G proteins versatile signaling elements that can respond quickly and precisely to changing environmental conditions.
Defects in G protein-mediated signaling pathways have been implicated in various diseases, including cancer, neurological disorders, and cardiovascular diseases. Therefore, understanding the function and regulation of GTP-binding proteins is essential for developing targeted therapeutic strategies.
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.
Pyrimidine nucleosides are organic compounds that consist of a pyrimidine base (a heterocyclic aromatic ring containing two nitrogen atoms and four carbon atoms) linked to a sugar molecule, specifically ribose or deoxyribose, via a β-glycosidic bond. The pyrimidine bases found in nucleosides can be cytosine (C), thymine (T), or uracil (U). When the sugar component is ribose, it is called a pyrimidine nucleoside, and when it is linked to deoxyribose, it is referred to as a deoxy-pyrimidine nucleoside. These molecules play crucial roles in various biological processes, particularly in the structure and function of nucleic acids such as DNA and RNA.
Serine is an amino acid, which is a building block of proteins. More specifically, it is a non-essential amino acid, meaning that the body can produce it from other compounds, and it does not need to be obtained through diet. Serine plays important roles in the body, such as contributing to the formation of the protective covering of nerve fibers (myelin sheath), helping to synthesize another amino acid called tryptophan, and taking part in the metabolism of fatty acids. It is also involved in the production of muscle tissues, the immune system, and the forming of cell structures. Serine can be found in various foods such as soy, eggs, cheese, meat, peanuts, lentils, and many others.
Nucleoside transport proteins (NTTs) are membrane-bound proteins responsible for the facilitated diffusion of nucleosides and related deoxynucleosides across the cell membrane. These proteins play a crucial role in the uptake of nucleosides, which serve as precursors for DNA and RNA synthesis, as well as for the salvage of nucleotides in the cell.
There are two main types of NTTs: concentrative (or sodium-dependent) nucleoside transporters (CNTs) and equilibrative (or sodium-independent) nucleoside transporters (ENTs). CNTs mainly facilitate the uptake of nucleosides against a concentration gradient, using the energy derived from the sodium ion gradient. In contrast, ENTs mediate bidirectional transport, allowing for the equalization of intracellular and extracellular nucleoside concentrations.
Nucleoside transport proteins have been identified in various organisms, including humans, and are involved in numerous physiological processes, such as cell proliferation, differentiation, and survival. Dysregulation of NTTs has been implicated in several pathological conditions, including cancer and viral infections, making them potential targets for therapeutic intervention.
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.
Gel chromatography is a type of liquid chromatography that separates molecules based on their size or molecular weight. It uses a stationary phase that consists of a gel matrix made up of cross-linked polymers, such as dextran, agarose, or polyacrylamide. The gel matrix contains pores of various sizes, which allow smaller molecules to penetrate deeper into the matrix while larger molecules are excluded.
In gel chromatography, a mixture of molecules is loaded onto the top of the gel column and eluted with a solvent that moves down the column by gravity or pressure. As the sample components move down the column, they interact with the gel matrix and get separated based on their size. Smaller molecules can enter the pores of the gel and take longer to elute, while larger molecules are excluded from the pores and elute more quickly.
Gel chromatography is commonly used to separate and purify proteins, nucleic acids, and other biomolecules based on their size and molecular weight. It is also used in the analysis of polymers, colloids, and other materials with a wide range of applications in chemistry, biology, and medicine.
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.
Crystallization is a process in which a substance transitions from a liquid or dissolved state to a solid state, forming a crystal lattice. In the medical context, crystallization can refer to the formation of crystals within the body, which can occur under certain conditions such as changes in pH, temperature, or concentration of solutes. These crystals can deposit in various tissues and organs, leading to the formation of crystal-induced diseases or disorders.
For example, in patients with gout, uric acid crystals can accumulate in joints, causing inflammation, pain, and swelling. Similarly, in nephrolithiasis (kidney stones), minerals in the urine can crystallize and form stones that can obstruct the urinary tract. Crystallization can also occur in other medical contexts, such as in the formation of dental calculus or plaque, and in the development of cataracts in the eye.
Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.
In this process:
1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.
EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.
DNA primers are short single-stranded DNA molecules that serve as a starting point for DNA synthesis. They are typically used in laboratory techniques such as the polymerase chain reaction (PCR) and DNA sequencing. The primer binds to a complementary sequence on the DNA template through base pairing, providing a free 3'-hydroxyl group for the DNA polymerase enzyme to add nucleotides and synthesize a new strand of DNA. This allows for specific and targeted amplification or analysis of a particular region of interest within a larger DNA molecule.
Phosphates, in a medical context, refer to the salts or esters of phosphoric acid. Phosphates play crucial roles in various biological processes within the human body. They are essential components of bones and teeth, where they combine with calcium to form hydroxyapatite crystals. Phosphates also participate in energy transfer reactions as phosphate groups attached to adenosine diphosphate (ADP) and adenosine triphosphate (ATP). Additionally, they contribute to buffer systems that help maintain normal pH levels in the body.
Abnormal levels of phosphates in the blood can indicate certain medical conditions. High phosphate levels (hyperphosphatemia) may be associated with kidney dysfunction, hyperparathyroidism, or excessive intake of phosphate-containing products. Low phosphate levels (hypophosphatemia) might result from malnutrition, vitamin D deficiency, or certain diseases affecting the small intestine or kidneys. Both hypophosphatemia and hyperphosphatemia can have significant impacts on various organ systems and may require medical intervention.
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.
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.
Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.
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.
Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.
PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.
Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.
Two-dimensional (2D) gel electrophoresis is a type of electrophoretic technique used in the separation and analysis of complex protein mixtures. This method combines two types of electrophoresis – isoelectric focusing (IEF) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) – to separate proteins based on their unique physical and chemical properties in two dimensions.
In the first dimension, IEF separates proteins according to their isoelectric points (pI), which is the pH at which a protein carries no net electrical charge. The proteins are focused into narrow zones along a pH gradient established within a gel strip. In the second dimension, SDS-PAGE separates the proteins based on their molecular weights by applying an electric field perpendicular to the first dimension.
The separated proteins form distinct spots on the 2D gel, which can be visualized using various staining techniques. The resulting protein pattern provides valuable information about the composition and modifications of the protein mixture, enabling researchers to identify and compare different proteins in various samples. Two-dimensional gel electrophoresis is widely used in proteomics research, biomarker discovery, and quality control in protein production.
A cell membrane, also known as the plasma membrane, is a thin semi-permeable phospholipid bilayer that surrounds all cells in animals, plants, and microorganisms. It functions as a barrier to control the movement of substances in and out of the cell, allowing necessary molecules such as nutrients, oxygen, and signaling molecules to enter while keeping out harmful substances and waste products. The cell membrane is composed mainly of phospholipids, which have hydrophilic (water-loving) heads and hydrophobic (water-fearing) tails. This unique structure allows the membrane to be flexible and fluid, yet selectively permeable. Additionally, various proteins are embedded in the membrane that serve as channels, pumps, receptors, and enzymes, contributing to the cell's overall functionality and communication with its environment.
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.
Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).
The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.
There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.
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.
Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.
Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.
"Pseudomonas aeruginosa" is a medically important, gram-negative, rod-shaped bacterium that is widely found in the environment, such as in soil, water, and on plants. It's an opportunistic pathogen, meaning it usually doesn't cause infection in healthy individuals but can cause severe and sometimes life-threatening infections in people with weakened immune systems, burns, or chronic lung diseases like cystic fibrosis.
P. aeruginosa is known for its remarkable ability to resist many antibiotics and disinfectants due to its intrinsic resistance mechanisms and the acquisition of additional resistance determinants. It can cause various types of infections, including respiratory tract infections, urinary tract infections, gastrointestinal infections, dermatitis, and severe bloodstream infections known as sepsis.
The bacterium produces a variety of virulence factors that contribute to its pathogenicity, such as exotoxins, proteases, and pigments like pyocyanin and pyoverdine, which aid in iron acquisition and help the organism evade host immune responses. Effective infection control measures, appropriate use of antibiotics, and close monitoring of high-risk patients are crucial for managing P. aeruginosa infections.
Equilibrative Nucleoside Transporter 1 (ENT1), also known as SLC29A1, is a protein that functions as a membrane transport protein. It is responsible for the facilitated diffusion of nucleosides and some related drugs across the cell membrane. The term "equilibrative" refers to the fact that this transporter moves substrates down their concentration gradient, meaning it facilitates the movement of molecules from an area of high concentration to an area of low concentration. ENT1 is widely expressed in various tissues, including the liver, kidney, intestine, and brain, playing a crucial role in nucleoside homeostasis and the cellular uptake of nucleoside-analog drugs used in cancer chemotherapy.
Uridine diphosphate (UDP) is a nucleotide diphosphate that consists of a pyrophosphate group, a ribose sugar, and the nucleobase uracil. It plays a crucial role as a coenzyme in various biosynthetic reactions, including the synthesis of glycogen, proteoglycans, and other polysaccharides. UDP is also involved in the detoxification of bilirubin, an end product of hemoglobin breakdown, by converting it to a water-soluble form that can be excreted through the bile. Additionally, UDP serves as a precursor for the synthesis of other nucleotides and their derivatives.
A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.
A 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.
Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).
The Western blotting procedure involves several steps:
1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.
Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.
Alkyl and aryl transferases are a group of enzymes that catalyze the transfer of alkyl or aryl groups from one molecule to another. These enzymes play a role in various biological processes, including the metabolism of drugs and other xenobiotics, as well as the biosynthesis of certain natural compounds.
Alkyl transferases typically catalyze the transfer of methyl or ethyl groups, while aryl transferases transfer larger aromatic rings. These enzymes often use cofactors such as S-adenosylmethionine (SAM) or acetyl-CoA to donate the alkyl or aryl group to a recipient molecule.
Examples of alkyl and aryl transferases include:
1. Methyltransferases: enzymes that transfer methyl groups from SAM to various acceptor molecules, such as DNA, RNA, proteins, and small molecules.
2. Histone methyltransferases: enzymes that methylate specific residues on histone proteins, which can affect chromatin structure and gene expression.
3. N-acyltransferases: enzymes that transfer acetyl or other acyl groups to amino groups in proteins or small molecules.
4. O-acyltransferases: enzymes that transfer acyl groups to hydroxyl groups in lipids, steroids, and other molecules.
5. Arylsulfatases: enzymes that remove sulfate groups from aromatic rings, releasing an alcohol and sulfate.
6. Glutathione S-transferases (GSTs): enzymes that transfer the tripeptide glutathione to electrophilic centers in xenobiotics and endogenous compounds, facilitating their detoxification and excretion.
A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.
The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.
The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.
In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.
"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.
Polyisoprenyl phosphates are a type of organic compound that play a crucial role in the biosynthesis of various essential biomolecules in cells. They are formed by the addition of isoprene units, which are five-carbon molecules with a branched structure, to a phosphate group.
In medical terms, polyisoprenyl phosphates are primarily known for their role as intermediates in the biosynthesis of dolichols and farnesylated proteins. Dolichols are long-chain isoprenoids that function as lipid carriers in the synthesis of glycoproteins, which are proteins that contain carbohydrate groups attached to them. Farnesylated proteins, on the other hand, are proteins that have been modified with a farnesyl group, which is a 15-carbon isoprenoid. This modification plays a role in the localization and function of certain proteins within the cell.
Abnormalities in the biosynthesis of polyisoprenyl phosphates and their downstream products have been implicated in various diseases, including cancer, neurological disorders, and genetic syndromes. Therefore, understanding the biology and regulation of these compounds is an active area of research with potential therapeutic implications.
Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.
In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.
Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.
Mitochondria are specialized structures located inside cells that convert the energy from food into ATP (adenosine triphosphate), which is the primary form of energy used by cells. They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of chemical energy. Mitochondria are also involved in various other cellular processes, such as signaling, differentiation, and apoptosis (programmed cell death).
Mitochondria have their own DNA, known as mitochondrial DNA (mtDNA), which is inherited maternally. This means that mtDNA is passed down from the mother to her offspring through the egg cells. Mitochondrial dysfunction has been linked to a variety of diseases and conditions, including neurodegenerative disorders, diabetes, and aging.
Pyrophosphatases are enzymes that catalyze the hydrolysis or cleavage of pyrophosphate (PPi) into two inorganic phosphate (Pi) molecules. This reaction is essential for many biochemical processes, such as energy metabolism and biosynthesis pathways, where pyrophosphate is generated as a byproduct. By removing the pyrophosphate, pyrophosphatases help drive these reactions forward and maintain the thermodynamic equilibrium.
There are several types of pyrophosphatases found in various organisms and cellular compartments, including:
1. Inorganic Pyrophosphatase (PPiase): This enzyme is widely distributed across all kingdoms of life and is responsible for hydrolyzing inorganic pyrophosphate into two phosphates. It plays a crucial role in maintaining the cellular energy balance by ensuring that the reverse reaction, the formation of pyrophosphate from two phosphates, does not occur spontaneously.
2. Nucleotide Pyrophosphatases: These enzymes hydrolyze the pyrophosphate bond in nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs), converting them into nucleoside monophosphates (NMPs) or deoxynucleoside monophosphates (dNMPs). This reaction is important for regulating the levels of NTPs and dNTPs in cells, which are necessary for DNA and RNA synthesis.
3. ATPases and GTPases: These enzymes belong to a larger family of P-loop NTPases that use the energy released from pyrophosphate bond hydrolysis to perform mechanical work or transport ions across membranes. Examples include the F1F0-ATP synthase, which synthesizes ATP using a proton gradient, and various molecular motors like myosin, kinesin, and dynein, which move along cytoskeletal filaments.
Overall, pyrophosphatases are essential for maintaining cellular homeostasis by regulating the levels of nucleotides and providing energy for various cellular processes.
UDP-glucose 4-epimerase (UGE) is an enzyme that catalyzes the reversible interconversion of UDP-galactose and UDP-glucose, two important nucleotide sugars involved in carbohydrate metabolism. This enzyme plays a crucial role in maintaining the balance between these two molecules, which are essential for the synthesis of various glycoconjugates, such as glycoproteins and proteoglycans. UGE is widely distributed in nature and has been identified in various organisms, including humans. In humans, deficiency or mutations in this enzyme can lead to a rare genetic disorder known as galactosemia, which is characterized by an impaired ability to metabolize the sugar galactose, resulting in several health issues.
Nucleoside-diphosphate kinase
Diphosphate-purine nucleoside kinase
NME1
Adenylate kinase
NME2
NME8
Nucleotide exchange factor
Telomeric repeat-binding factor 1
Joyoti Basu
NME4
Acetyl-CoA
RAR-related orphan receptor alpha
Treatment of lung cancer
Kinase
Michael Fischbach
NME3
MOBKL3
Thymidine kinase in clinical chemistry
Uridine triphosphate
Nucleotide salvage
Ribonucleotide
GNG4
GNG13
GNGT1
GNG12
GNG5
GNB4
GNG3
GNG2
GNGT2
Nucleoside-diphosphate kinase - Wikipedia
3EE3: Crystal Structure Of Acanthamoeba Polyphaga Mimivirus Nucleoside Diphosphate Kinase Complexed With Cdp
RCSB PDB - 3Q8V: Crystal structure of Staphylococcus aureus nucleoside diphosphate kinase complexed with UDP
SCOP 1.73: Protein: Nucleoside diphosphate kinase, NDK
1b99.1 | SWISS-MODEL Template Library
A Structural mechanism for dimeric to tetrameric oligomer conversion in {\it Halomonas} sp. nucleoside diphosphate kinase
2BEF: Crystal Structure Of Ndp Kinase Complexed With Mg, Adp, And Bef3
Histidine 117 in the His-Gly-Ser-Asp motif is Required for the Biochemical Activities of Nucleoside Diphosphate Kinase of
Ramaswami Publications
SCOPe 2.08: Domain d1wkka : 1wkk A
Increased c‑SRC expression is involved in acquired resistance to lenvatinib in hepatocellular carcinoma
NM23-H2/NME2 Antibody (1D3) (H00004831-M06): Novus Biologicals
Paths to Guanine and Adenine Nucleotides - Biochemistry Course
Comparative Biochem Flashcards
negative regulation of myeloid cell differentiation - Ontology Report - Rat Genome Database
SMART: NDK domain annotation
Applied Biosciences | Free Full-Text | Gene Drive: Past, Present and Future Roads to Vertebrate Biocontrol
NME2 (NM 001018139) Human Tagged ORF Clone - RC200680 | OriGene
SBF1 (NM 002972) Human Untagged Clone - OriGene
Evaluation of Vimentin as a Potential Poor Prognostic Indicator and Salivary Biomarker for Oral Cancers and Pre-Cancers by Mass...
Gemcitabine - Gemzar® - GlobalRPH
Publikationen der Gruppe | Max-Planck-Institut für Molekulare Pflanzenphysiologie
G2P[4]-RotaTeq Reassortant Rotavirus in Vaccinated Child, United States - Volume 21, Number 11-November 2015 - Emerging...
Publikationen von Roosa Laitinen | Max-Planck-Institut für Molekulare Pflanzenphysiologie
Periodontal Medicine: Impact of Periodontal Status on Pregnancy Outcomes and Carcinogenesis | IntechOpen
nodal1 Literature
BiGG Reaction NDPK7 in iECSP 1301
BiGG Reaction NDPK8 in iETEC 1333
WikiGenes
NDPK8
- NDPK activities maintain an equilibrium between the concentrations of different nucleoside triphosphates such as, for example, when guanosine triphosphate (GTP) produced in the citric acid (Krebs) cycle is converted to adenosine triphosphate (ATP). (wikipedia.org)
- NDPK are found in all cells, displaying not much specificity towards the types of nucleoside bases and are capable of accepting nucleotides and deoxyribonucleotides as substrates or donors. (wikipedia.org)
- NDPK are involved in the synthesis of nucleoside triphosphates (NTP), such as guanosine triphosphate (GTP), cytidine triphosphate (CTP) and uridine triphosphate (UTP), thymidine triphosphate (TTP). (wikipedia.org)
- NDPK has also been discovered to act as a protein histidine kinase, which involves a reversible histidine phosphorylation as a well-known regulatory signal. (wikipedia.org)
- These oligomeric proteins exhibit nucleoside diphosphate kinase (NDPK) activity that catalyzes nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates. (embl.de)
- nucleoside diphosphate kinase (NDPK). (powerofpositivity.com)
- The Nme gene/protein family of nucleoside diphosphate kinases (NDPK) was originally named after its member Nm23-H1/Nme1, the first identified metastasis suppressor. (bvsalud.org)
- Biochemical studies showed that hNME1 is regulated by CoA through both covalent and non-covalent binding, which leads to a decrease in the hNME1 nucleoside diphosphate kinase (NDPK) activity. (bvsalud.org)
Proteins1
- Many of the expanding roles of nucleoside diphosphate kinase have been attributed to its ability to interact with other proteins. (dundee.ac.uk)
Protein kinase3
- However, consumption of ATP would definitely influence the cellular energy balance, which brings upon the regulation of AMP-activated protein kinase (AMPK). (wikipedia.org)
- One proposal is an interaction with the cellular energy sensor AMP-activated protein kinase, and here, we apply the simple eukaryotic organism, Dictyostelium discoideum as a test model. (dundee.ac.uk)
- It phosphorylates first to monophosphate form by a viral-encoded protein kinase homologue, and then to diphosphate and triphosphate forms by cellular kinases. (medscape.com)
Enzyme4
- Nucleoside diphosphate kinase (Ndk) is an important enzyme that generates nucleoside triphosphates (NTPs) or their deoxy derivatives by terminal phosphotransfer from an NTP such as ATP or GTP to any nucleoside diphosphate or its deoxy derivative. (embl.de)
- Inhibition of this enzyme by the diphosphate nucleoside causes a reduction in the concentrations of deoxynucleotides, including dCTP. (globalrph.com)
- A new subfamily of short bacterial adenylate kinases with the Mycobacterium tuberculosis enzyme as a model: a predictive and experimental study. (rhea-db.org)
- A sequence comparison with 52 different forms of adenylate kinases (AK) suggests that the enzyme from M. tuberculosis belongs to a new subfamily of 'short' bacterial AKs. (rhea-db.org)
Mitochondrial1
- 2023. J. Cell Biol.https://doi.org/10.1083/jcb.202301091) report that a nucleoside diphosphate kinase, NME3, facilitates mitochondrial tethering prior to fusion through its direct membrane-binding and hexamerization but not its kinase activity. (bvsalud.org)
NM232
- NM23-NDP kinase. (embl.de)
- Lastly, ethanol increased the expression of Kiss1 metastasis-suppressor and the metastasis suppressor Nm23/nucleoside diphosphate kinase. (iiarjournals.org)
Adenylate kinase3
- Expression of nucleoside diphosphate kinase, mitochondria-associated adenylate kinase, and several mitochondria-associated creatine kinase isozymes was highest in the outer retina, whereas expression of cytosolic adenylate kinase and brain creatine kinase was higher in the cones, horizontal cells, and amacrine cells indicating the diversity of ATP-buffering strategies among retinal neurons. (molvis.org)
- The characterization of human adenylate kinases 7 and 8 demonstrates differences in kinetic parameters and structural organization among the family of adenylate kinase isoenzymes. (rhea-db.org)
- Differences in expression profiles, substrate specificities, kinetic properties and subcellular localization among the AK (adenylate kinase) isoenzymes have been shown to be important for maintaining a proper adenine nucleotide composition for many different cell functions. (rhea-db.org)
Triphosphate4
- Nucleoside diphosphate kinase activity involves the transfer of the γ-phosphate of nucleoside triphosphate (NTP) to nucleoside diphosphate (NDP), where N1 and N2 can be ribo- or deoxyribonucleosides. (wikipedia.org)
- Gemcitabine is metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. (globalrph.com)
- The cytotoxic effect of gemcitabine is attributed to a combination of two actions of the diphosphate and the triphosphate nucleosides, which leads to inhibition of DNA synthesis. (globalrph.com)
- The reduction in the intracellular concentration of dCTP (by the action of the diphosphate) enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). (globalrph.com)
Nucleotide4
- Nucleoside-diphosphate kinases (NDPKs, also NDP kinase, (poly)nucleotide kinases and nucleoside diphosphokinases) are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) in a reversible manner to produce nucleotide triphosphates. (wikipedia.org)
- Catalytic mechanism of nucleoside diphosphate kinase investigated using nucleotide analogues, viscosity effects, and X-ray crystallography. (expasy.org)
- Nucleoside diphosphate kinase (NDK), which is widely conserved in both prokaryotes and eukaryotes, maintains a balanced pool of nucleotide triphosphates and their deoxy derivatives. (openbiochemistryjournal.com)
- Synthesis of 8-hydroxy and 8-mercapto derivatives of acyclic adenine nucleoside and nucleotide analogs. (cas.cz)
Triphosphates4
- Maintenance of the level of nucleoside triphosphates (NTPs) as well as their corresponding deoxy derivatives (dNTPs) is crucial to all growth and developmental processes. (openbiochemistryjournal.com)
- These are enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates. (embl.de)
- Nucleoside diphosphate kinases ( EC 2.7.4.6 ) (NDK) are enzymes required for the synthesis of nucleoside triphosphates (NTP) other than ATP. (embl.de)
- First, gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for catalyzing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis. (globalrph.com)
Dictyostelium2
- The hexameric NDP kinase from Dictyostelium discoideum displays one single, irreversible differential scanning calorimetry peak (Tm 62 degrees C) over a broad protein concentration, indicating a single step denaturation. (protabank.org)
- The NDP kinase from Escherichia coli behaves like the P105G mutant of the Dictyostelium NDP kinase. (protabank.org)
NTPs1
- generally, kinases bring in NTPs for nucleic acid synthesis. (wikipedia.org)
Tetrameric1
- Thermal stability of hexameric and tetrameric nucleoside diphosphate kinases. (protabank.org)
Gene1
- Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by this gene) isoforms. (novusbio.com)
Bacterial2
- Nucleoside diphosphate kinase: role in bacterial growth, virulence, cell signalling and polysaccharide synthesis. (embl.de)
- The eukaryotic nucleoside diphosphate (NDP) kinases are hexamers, while the bacterial NDP kinases are tetramers made of small, single domain subunits. (protabank.org)
Catalytic1
- Nucleoside diphosphate kinases (NDK) are characterized by high catalytic turnover rates and diverse substrate specificity. (rcsb.org)
Phosphoglycerate1
- Global mapping of protein-metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity. (mpg.de)
Roles1
- Affinity purification with metabolomic and proteomic analysis unravels diverse roles of nucleoside diphosphate kinases. (mpg.de)
Subcellular localization1
- We found that cytoplasmic NDP kinase can be separated into two populations according to subcellular localization and response to extracellular stimuli. (liberty.edu)
Inhibits2
- Lenvatinib is an oral multi-kinase inhibitor that inhibits mainly vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptor (PDGFR) α, c-KIT, and RET ( 11 ). (spandidos-publications.com)
- Transfection of cells with activated Rac mimics, whereas expression of dominant negative Rac inhibits, the effects of extracellular stimulation on the translocation of NDP kinase to the cell cortex. (liberty.edu)
Sequence1
- IC1 has a unique primary structure, the N-terminal part is homologous to the sequence of thioredoxin, the middle part consists of three repetitive sequences homologous to the sequence of nucleoside diphosphate kinase, and the C-terminal part contains a high proportion of negatively charged glutamic acid residues. (embl.de)
Regulates1
- and Otero, Angela de S., "Receptor Activation Regulates Cortical, but not Vesicular Localization of NDP Kinase" (2003). (liberty.edu)
Cellular2
- Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. (molvis.org)
- Thus, the localization of the two NDP kinase pools identified here is regulated independently by distinct cellular components: the appearance of cortical NDP kinase is a consequence of Rac activation, whereas vesicular NDP kinase is responsive to microtubule dynamics and nucleotides, in particular GTP. (liberty.edu)
Liver1
- All non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized in the liver by CYP3A isoenzymes. (medscape.com)
Suggests1
- This suggests that MGCs utilize TCA cycle anaplerosis and cataplerosis to generate GTP and ~P transferring kinases to produce ATP that supports MGC energy requirements. (molvis.org)
Nucleotides1
- Binding of NDP kinase to this fraction is reduced by ATP and abolished by GTP, as well as guanine nucleotides that are NDP kinase substrates. (liberty.edu)
Intracellular2
- Another pool of NDP kinase accumulates independently of stimulation around intracellular vesicles. (liberty.edu)
- These results suggest that in fibroblasts NDP kinase participates in Racrelated cortical events and in GTP-dependent processes linked to intracellular vesicle trafficking. (liberty.edu)
Differential1
- The thermostability of NDP kinases of each class was studied by differential scanning calorimetry and biochemical methods. (protabank.org)
Cell2
- In cell-free assays NDP kinase binds tightly to membrane vesicles associated with taxol-stabilized microtubules. (liberty.edu)
- Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. (cdc.gov)
Crucial1
- Lenvatinib, a multi‑kinase inhibitor, serves a crucial role in the treatment of unresectable hepatocellular carcinoma (HCC). (spandidos-publications.com)
Important1
- The detailed study of their thermostability is important, since biological effects of thermolabile NDP kinases have been described in several organisms. (protabank.org)
Domain1
- They all possess nucleoside diphosphate kinase domain (NDK). (bvsalud.org)