GTP Pyrophosphokinase
Thiamin Pyrophosphokinase
Diphosphotransferases
Ribose-Phosphate Pyrophosphokinase
Pyrithiamine
Thiamine Pyrophosphatase
Dihydropteroate Synthase
Thiamine Monophosphate
Phosphotransferases
Thiamine Pyrophosphate
Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis. (1/14)
Catalytic and regulatory domains of the Rel/Spo homolog of Streptococcus equisimilis affecting (p)ppGpp synthesis and degradation activities have been defined, and opposing activities of the purified protein and its fragments have been compared. Two major domains of the 739-residue Rel(Seq) protein are defined by limited proteolytic digestion. In vitro assays of the purified N-terminal half-protein reveal synthesis of (p)ppGpp by an ATP-GTP 3'-pyrophosphotransferase as well as an ability to degrade (p)ppGpp by a Mn(2+)-dependent 3'-pyrophosphohydrolase. Removal of the C-terminal half-protein has reciprocal regulatory effects on the activities of the N-terminal half-protein. Compared to the full-length protein, deletion activates (p)ppGpp synthesis specific activity about 12-fold and simultaneously inhibits (p)ppGpp degradation specific activity about 150-fold to shift the balance of the two activities in favor of synthesis. Cellular (p)ppGpp accumulation behavior is consistent with these changes. The bifunctional N-terminal half-protein can be further dissected into overlapping monofunctional subdomains, since purified peptides display either degradation activity (residues 1 to 224) or synthetic activity (residues 79 to 385) in vitro. These assignments can also apply to RelA and SpoT. The ability of Rel(Seq) to mediate (p)ppGpp accumulation during amino acid starvation in S. equisimilis is absent when the protein is expressed ectopically in Escherichia coli. Fusing the N-terminal half of Rel(Seq) with the C-terminal domain of RelA creates a chimeric protein that restores the stringent response in E. coli by inhibiting unregulated degradation and restoring regulated synthetic activity. Reciprocal intramolecular regulation of the dual activities may be a general intrinsic feature of Rel/Spo homolog proteins. (+info)Modulation of Borrelia burgdorferi stringent response and gene expression during extracellular growth with tick cells. (2/14)
Borrelia burgdorferi N40 multiplied extracellularly when it was cocultured with tick cells in L15BS medium, a medium which by itself did not support B. burgdorferi N40 growth. Growth of B. burgdorferi N40 in the presence of tick cells was associated with decreased production of (p)ppGpp, the stringent response global regulator, a fourfold decrease in relA/spoT mRNA, an eightfold net decrease in bmpD mRNA, and a fourfold increase in rpsL-bmpD mRNA compared to growth of B. burgdorferi in BSK-H medium. As a result, the polycistronic rpsL-bmpD mRNA level increased from 3 to 100% of the total bmpD message. These observations demonstrate that there are reciprocal interactions between B. burgdorferi and tick cells in vitro and indicate that the starvation-associated stringent response mediated by (p)ppGpp present in B. burgdorferi growing in BSK-H medium is ameliorated in B. burgdorferi growing in coculture with tick cell lines. These results suggest that this system can provide a useful model for identifying genes controlling interactions of B. burgdorferi with tick cells in vitro when it is coupled with genetic methods to isolate and complement B. burgdorferi mutants. (+info)Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response [corrected]. (3/14)
Enzymes of the Rel/Spo family enable bacteria to survive prolonged periods of nutrient limitation by producing an intracellular signaling alarmone, (p)ppGpp, which triggers the so-called stringent response. Both the synthesis of (p)ppGpp from ATP and GDP(GTP), and its hydrolysis to GDP(GTP) and pyrophosphate, are catalyzed by Rel/Spo proteins. The 2.1 A crystal structure of the bifunctional catalytic fragment of the Rel/Spo homolog from Streptococcus dysgalactiae subsp. equisimilis, Rel(Seq), reveals two conformations of the enzyme corresponding to known reciprocal activity states: (p)ppGpp-hydrolase-OFF/(p)ppGpp-synthetase-ON and hydrolase-ON/synthetase-OFF. The hydrolase and synthetase domains bear remarkable similarities to the catalytic domains of the cyclic phosphodiesterase and nucleotidyltransferase superfamilies, respectively. The active sites, separated by more than 30 A, contain bound nucleotides including an unusual (p)ppGpp derivative, GDP-2':3'-cyclic monophosphate. Reciprocal regulation of the antagonistic catalytic activities, suggested by the structure, is supported by mutagenesis experiments and appears to involve ligand-induced signal transmission between the two active sites. (+info)Characterization of the tRNA and ribosome-dependent pppGpp-synthesis by recombinant stringent factor from Escherichia coli. (4/14)
Stringent factor is a ribosome-dependent ATP:GTP pyrophosphoryl transferase that synthesizes (p)ppGpp upon nutrient deprivation. It is activated by unacylated tRNA in the ribosomal amino-acyl site (A-site) but it is unclear how activation occurs. A His-tagged stringent factor was isolated by affinity-chromatography and precipitation. This procedure yielded a protein of high purity that displayed (a) a low endogenous pyrophosphoryl transferase activity that was inhibited by the antibiotic tetracycline; (b) a low ribosome-dependent activity that was inhibited by the A-site specific antibiotics thiostrepton, micrococcin, tetracycline and viomycin; (c) a tRNA- and ribosome-dependent activity amounting to 4500 pmol pppGpp per pmol stringent factor per minute. Footprinting analysis showed that stringent factor interacted with ribosomes that contained tRNAs bound in classical states. Maximal activity was seen when the ribosomal A-site was presaturated with unacylated tRNA. Less tRNA was required to reach maximal activity when stringent factor and unacylated tRNA were added simultaneously to ribosomes, suggesting that stringent factor formed a complex with tRNA in solution that had higher affinity for the ribosomal A-site. However, tRNA-saturation curves, performed at two different ribosome/stringent factor ratios and filter-binding assays, did not support this hypothesis. (+info)Differential stringent responses of Streptomyces coelicolor M600 to starvation of specific nutrients. (5/14)
This study focused on the involvement of the unusual nucleotide (p)ppGpp, a stringent factor, during the morphological and physiological differentiation of Streptomyces coelicolor. Two genes, relA and rshA, were disrupted to demonstrate the roles of the stringent factor in the differentiation. The intracellular concentration of (p)ppGpp in the wild-type (M600) and disrupted mutants was measured in relation to the intentional starvation of a specific nutrient such as carbon, nitrogen, and phosphate or the in situ depletion of nutrients in a batch culture. As a result, it was found that the morphological characteristic of the deltarelA mutant was a bld phenotype forming condensed mycelia, whereas the deltarshA mutant grew fast-forming spores and straightforward mycelia. In both mutants, the production of actinorhodin (Act) was completely abolished, yet the undecylprodigiosin (Red) production was increased. Intracellular (p)ppGpp was detected in the deltarelA mutant in the case of limited phosphate, yet not with limited carbon or nitrogen sources. In contrast, (p)ppGpp was produced in the deltarshA mutant under limited carbon and nitrogen conditions. Therefore, (p)ppGpp in S. coelicolor was found to be selectively regulated by either the RelA or RshA protein, which was differentially expressed in response to the specific nutrient limitation. These results were also supported by the in situ ppGpp production during a batch culture. Furthermore, it is suggested that RelA and RshA are bifunctional proteins that possess the ability to both synthesize and hydrolyze (p)ppGpp. (+info)Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase. (6/14)
(+info)The stringent response is required for full virulence of Mycobacterium tuberculosis in guinea pigs. (7/14)
(+info)Characterization of the relA1 mutation and a comparison of relA1 with new relA null alleles in Escherichia coli. (8/14)
The most widely studied "relaxed" mutant of the relA locus, the relA1 allele, is shown here to consist of an IS2 insertion between the 85th and 86th codons of the otherwise wild-type relA structural gene, which normally encodes a 743-amino acid (84 kDa) protein. The RelA protein is a ribosome-dependent ATP:GTP (GDP) pyrophosphoryltransferase that is activated during the stringent response to amino acid starvation and thereby occasions the accumulation of guanosine 3',5'-bispyrophosphate (ppGpp). We propose that the IS2 insertion functionally splits the RelA protein into two (alpha and beta) peptide fragments which can complement each other in trans to yield residual ppGpp synthetic activity; neither fragment shows this activity when expressed alone. Cell strains with a single copy relA null allele show physiological behavior that is much the same as relA1 mutant strains. Both relA1 and relA null strains accumulate ppGpp during glucose starvation and do not accumulate ppGpp during the stringent response. The presence of ppGpp in verifiable relA null strains is interpreted as unequivocal evidence for an alternate route of ppGpp synthesis that exists in addition to the relA-dependent reaction. (+info)GTP Pyrophosphokinase (or GTP-PK) is an enzyme that plays a crucial role in the regulation of cell growth and proliferation. It catalyzes the conversion of GTP (guanosine triphosphate) to GDP (guanosine diphosphate) and pyrophosphate, using ATP as a phosphate donor. This reaction is essential for various cellular processes, including protein synthesis, signal transduction, and vesicle trafficking.
There are two main types of GTP Pyrophosphokinase:
1. Alpha (α) GTP-PK: This enzyme is involved in the regulation of small G proteins, such as Ras and Rho, which play critical roles in signal transduction pathways that control cell growth, differentiation, and motility. Mutations in α-GTP-PK can lead to abnormal activation of these signaling pathways, contributing to the development of various types of cancer.
2. Beta (β) GTP-PK: This enzyme is primarily involved in the regulation of protein synthesis and nucleotide metabolism. It plays a critical role in the initiation phase of protein synthesis by activating eukaryotic initiation factor 2 (eIF2), which is required for the binding of methionyl-tRNA to the ribosome during translation.
Dysregulation of GTP Pyrophosphokinase activity has been implicated in various diseases, including cancer and neurological disorders.
Thiamin pyrophosphokinase (TPK) is an enzyme that plays a crucial role in the metabolism of thiamin, also known as vitamin B1. Thiamin is essential for the body's energy production and nerve function. TPK catalyzes the conversion of thiamin into its active form, thiamin pyrophosphate (TPP), by adding two phosphate groups to thiamin. This reaction is the rate-limiting step in the synthesis of TPP, which serves as a cofactor for several enzymes involved in carbohydrate metabolism, particularly in the process of decarboxylation of alpha-keto acids.
TPK exists in two isoforms: cytoplasmic and mitochondrial. The cytoplasmic form (cTPK) is primarily responsible for maintaining intracellular TPP levels, while the mitochondrial form (mTPK) helps regulate TPP concentrations within the mitochondria. Proper functioning of TPK is vital for overall cellular health and energy production, as well as for preventing neurological disorders associated with thiamin deficiency, such as beriberi and Wernicke-Korsakoff syndrome.
Diphosphotransferases are a group of enzymes that catalyze the transfer of a diphosphate group from a donor molecule to an acceptor molecule. These enzymes play important roles in various metabolic pathways, including the synthesis of nucleotides, lipids, and carbohydrates.
The systematic name for this type of reaction is "diphosphate-group transferase." Diphosphotransferases can be further classified based on the specific type of donor and acceptor molecules involved in the reaction. For example, nucleoside diphosphate kinases are a subclass of diphosphotransferases that transfer a diphosphate group from a nucleoside triphosphate (such as ATP) to a nucleoside diphosphate (such as ADP), generating two molecules of nucleoside triphosphate.
It's worth noting that while the term "diphosphotransferases" is sometimes used in the scientific literature, it is not a widely recognized or commonly used term in medical or biochemical nomenclature. Instead, enzymes are typically classified and named based on the specific reaction they catalyze, using standardized nomenclature systems such as the Enzyme Commission (EC) numbering system.
Thiamine, also known as vitamin B1, is a water-soluble vitamin that plays a crucial role in certain metabolic reactions, particularly in the conversion of carbohydrates into energy in the body. It is essential for the proper functioning of the heart, nerves, and digestive system. Thiamine acts as a cofactor for enzymes involved in the synthesis of neurotransmitters and the metabolism of carbohydrates, lipids, and proteins. Deficiency in thiamine can lead to serious health complications, such as beriberi (a disease characterized by peripheral neuropathy, muscle wasting, and heart failure) and Wernicke-Korsakoff syndrome (a neurological disorder often seen in alcoholics due to chronic thiamine deficiency). Thiamine is found in various foods, including whole grains, legumes, pork, beef, and fortified foods.
Ribose-Phosphate Pyrophosphokinase (PRPS): It is an enzyme involved in the metabolic pathway of nucleotide synthesis. The systematic name for this enzyme is ribose-5-phosphate:ATP phosphotransferase. This enzyme catalyzes the conversion of ribose-5-phosphate and ATP to ribose-1,5-bisphosphate and AMP, plus inorganic pyrophosphate (PPi).
The reaction is:
ribose-5-phosphate + ATP -> ribose-1,5-bisphosphate + AMP + PPi
This enzyme plays a crucial role in the synthesis of purine nucleotides, which are essential for DNA and RNA synthesis. Deficiency or mutations in this enzyme can lead to serious medical conditions such as hereditary sensory neuropathy (HSN) and Arts syndrome.
Pterins are a group of naturally occurring pigments that are derived from purines. They are widely distributed in various organisms, including bacteria, fungi, and animals. In humans, pterins are primarily found in the eye, skin, and hair. Some pterins have been found to play important roles as cofactors in enzymatic reactions and as electron carriers in metabolic pathways.
Abnormal levels of certain pterins can be indicative of genetic disorders or other medical conditions. For example, an excess of biopterin, a type of pterin, is associated with phenylketonuria (PKU), a genetic disorder that affects the body's ability to metabolize the amino acid phenylalanine. Similarly, low levels of neopterin, another type of pterin, can be indicative of immune system dysfunction or certain types of cancer.
Medical professionals may measure pterin levels in blood, urine, or other bodily fluids to help diagnose and monitor these conditions.
Pyrithiamine is not typically considered a medical term, but it is a chemical compound that has been used in scientific research. It's an antivitamin, specifically an analog of thiamine (vitamin B1), which means it can interfere with the metabolism of thiamine in the body.
Here's a more specific definition from a biochemical perspective:
Pyrithiamine is a synthetic organic compound with the formula C6H7N2O2S. It is an analog of thiamine, where the aminomethyl group of thiamine is replaced by a pyridine ring. This structural modification makes pyrithiamine unable to act as a vitamin, but it can still interact with the enzymes and transport proteins involved in thiamine metabolism. As a result, pyrithiamine has been used as a tool to study thiamine deficiency and its effects on various organisms, including mammals.
Please note that pyrithiamine is not a term commonly used in clinical medicine or patient care. If you have any concerns about vitamins, nutrition, or health-related topics, it's best to consult a healthcare professional for accurate information and advice tailored to your specific situation.
Thiamine pyrophosphatase (TPP) is an enzyme that catalyzes the hydrolysis of thiamine pyrophosphate (TPP), which is a cofactor involved in several important metabolic pathways, including carbohydrate metabolism and neurotransmitter synthesis.
The reaction catalyzed by TPP is:
thiamine pyrophosphate + H2O → thiamine + phosphate
TPP is also known as thiamine diphosphatase or vitamin B1 diphosphatase. Deficiency of this enzyme can lead to thiamine deficiency disorders such as beriberi and Wernicke-Korsakoff syndrome, which are characterized by neurological and cardiovascular symptoms.
Dihydropteroate synthase is a bacterial enzyme that plays a crucial role in the synthesis of folate, an essential nutrient for many organisms, including bacteria. The enzyme catalyzes the reaction between pteridine and para-aminobenzoic acid (pABA) to form dihydropteroate, which is then converted into folate.
Inhibition of this enzyme by drugs such as sulfonamides has been a successful strategy for developing antibiotics that target bacterial folate synthesis while sparing the host's metabolism. This makes dihydropteroate synthase an important target in the development of antimicrobial therapies.
Thiamine monophosphate (TMP) is a biochemical compound that is a derivative of thiamine (vitamin B1). It is a cofactor for several enzymes involved in key metabolic processes, particularly in the conversion of carbohydrates into energy. TMP plays an essential role in the metabolism of carbohydrates, amino acids, and neurotransmitters.
Thiamine monophosphate is formed when thiamine undergoes phosphorylation by the enzyme thiamine pyrophosphokinase. This reaction adds a phosphate group to the thiamine molecule, resulting in the formation of TMP. Thiamine monophosphate can then be further phosphorylated to form thiamine triphosphate (TTP) or dephosphorylated back to thiamine.
Deficiency in thiamine and its derivatives, including TMP, can lead to several medical conditions, such as beriberi, Wernicke-Korsakoff syndrome, and other neurological disorders. These conditions are often associated with impaired energy metabolism, nerve damage, and cognitive decline. Proper intake of thiamine through diet or supplementation is crucial for maintaining normal physiological functions and preventing these health issues.
Oxythiamine is not a medication or a condition, but rather a chemical compound. It is an oxidized form of thiamine (vitamin B1), which means it has been changed by the addition of oxygen molecules. Oxythiamine is used in research to study the effects of thiamine deficiency and to investigate the role of thiamine in various biological processes. It is not used as a medication in humans or animals.
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.
Thiamine pyrophosphate (TPP) is the active form of thiamine (vitamin B1) that plays a crucial role as a cofactor in various enzymatic reactions, particularly in carbohydrate metabolism. TPP is essential for the functioning of three key enzymes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. These enzymes are involved in critical processes such as the conversion of pyruvate to acetyl-CoA, the oxidative decarboxylation of alpha-ketoglutarate in the Krebs cycle, and the pentose phosphate pathway, which is important for generating reducing equivalents (NADPH) and ribose sugars for nucleotide synthesis. A deficiency in thiamine or TPP can lead to severe neurological disorders, including beriberi and Wernicke-Korsakoff syndrome, which are often observed in alcoholics due to poor nutrition and impaired thiamine absorption.
Aldehyde-lyases are a class of enzymes that catalyze the breakdown or synthesis of molecules involving an aldehyde group through a reaction known as lyase cleavage. This type of reaction results in the removal of a molecule, typically water or carbon dioxide, from the substrate.
In the case of aldehyde-lyases, these enzymes specifically catalyze reactions that involve the conversion of an aldehyde into a carboxylic acid or vice versa. These enzymes are important in various metabolic pathways and play a crucial role in the biosynthesis and degradation of several biomolecules, including carbohydrates, amino acids, and lipids.
The systematic name for this class of enzymes is "ald(e)hyde-lyases." They are classified under EC number 4.3.1 in the Enzyme Commission (EC) system.
List of MeSH codes (D08)
Evansella
GTP diphosphokinase
Ribose-phosphate diphosphokinase
SCOPe 2.08: Protein: Putative GTP pyrophosphokinase SP1097
B. subtilis Expression Data Browser
List of MeSH codes (D08) - Wikipedia
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Propagation of CcpA regulog to Lactococcus lactis subsp. cremoris MG1363
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Purines and pyrimidines
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Guanosine1
- An enzyme that catalyzes reversibly the transfer of a pyrophosphate group from ATP to the 3'-OH group of GDP or GTP with the formation of guanosine 3'-diphosphate 5'-diphosphate or guanosine 3'-diphosphate 5'-triphosphate and AMP . (nih.gov)
Protein1
- Following detailed studies of bacterial systems from the 1940s onwards, it was established that PYR and CG target the dihydrofolate reductase (DHFR) activity of the parasite's bifunctional DHFR-thymidylate synthetase (TS) protein, whereas the sulfa drugs affect the dihydropteroate synthetase (DHPS) activity of the bifunctional hydroxymethylpterin pyrophosphokinase (HPPK)-DHPS protein, all of these drugs acting as competitive inhibitors of the natural substrates. (medscape.com)
Factor1
- La enzima, también llamada factor estricto, está localizada en el gen reIA en cepas estrictas de bacterias. (bvsalud.org)
Domain1
- Thiamin pyrophosphokinase, thiamin-binding domain [Interproscan]. (ntu.edu.sg)