Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystathionine beta-synthase (CBS) is a unique heme-containing enzyme that catalyses a pyridoxal 5'-phosphate (PLP)-dependent condensation of serine and homocysteine to give cystathionine. Deficiency of CBS leads to homocystinuria, an inherited disease of sulfur amino acid metabolism characterised by increased levels of homocysteine and methionine and decreased levels of cysteine. Presently, more than 100 CBS mutations have been described which lead to homocystinuria with different degrees of severity in the patients. We have recently solved the crystal structure of a truncated form of this enzyme, which enables us to correlate some of these mutations with the structure.
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PMID:Structural insights into mutations of cystathionine beta-synthase. 1268 34

In this study, the phosphoproteome of Corynebacterium glutamicum, an industrially important soil bacterium of the Corynebacterium/Mycobacterium/Nocardia (CMN) group of Gram-positive bacteria, was investigated by two different detection methods: first, by in vivo radio-labeling using [(33)P]-phosphoric acid with subsequent autoradiography and second, by immunostaining with phosphoamino acid-specific monoclonal antibodies. After two-dimensional gel electrophoresis (2-DE), around 60 [(33)P]-labeled protein spots were visualized and around 90 antibody-decorated protein spots detected; 31 of the protein spots were detected with both methods. By peptide mass fingerprinting, 41 different proteins were identified, namely 5-enolpyruvylshikimate 3-phosphate synthase, aconitase, acyl-CoA carboxylase, acyl-CoA synthetase, ATP (synthase alpha- and beta-chain), carbamoyl-phosphate synthase, citrate synthase, cysteine synthase, DnaK, the elongation factors G, P, Ts and Tu, enolase, fructose bisphosphate aldolase, fumarase, Gap dehydrogenase, glutamine synthetase I, glycine hydroxymethyltransferase, GroEL2, GTPase, heat-inducible transcriptional repressor DnaJ2, inorganic pyrophosphatase, isocitrate dehydrogenase, ketol-acid reductoisomerase, lactate dehydrogenase, leucine-tRNA ligase, lipoamide dehydrogenase, methionine synthase, O-acetylhomoserine sulfhydrylase, pyruvate carboxylase, pyruvate kinase, pyruvate oxidase, ribosomal protein S1, RNA polymerase (beta-subunit), succinyl-CoA:CoA transferase, transketolase and UDP-N-acetylmuramoyl-L-alanine ligase, besides a hypothetical 35k protein and a hypothetical glucose kinase. Both detection techniques were used to create a phosphoproteome map. Additionally, the influence of nitrogen deprivation on the phosphoproteome of C. glutamicum was investigated.
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PMID:Towards a phosphoproteome map of Corynebacterium glutamicum. 1292 88

1. An enzyme from Escherichia coli 9723 that reduces adenosine 3'-phosphate 5'-sulphatophosphate to inorganic sulphite is described. Extracts of E. coli K(12) and Bacillus subtilis 1379 contain a similar enzyme. 2. This reductase and sulphite reductase (EC 1.8.1.2) of E. coli 9723, E. coli K(12) and of B. subtilis are repressed by growth in the presence of l-cystine. Cysteine synthase (EC 4.2.1.22) is unaffected. 3. Growth of E. coli 9723 on inorganic sulphite represses the sulphate-activating enzymes (EC 2.7.7.4 and 2.7.1.25) almost completely but has little effect on sulphite reductase. Growth on 0.042-0.056mm-l-cystine gives a similar result. 4. Such differential repression by cyst(e)ine prevents E. coli, when growing on sulphite, from synthesizing unnecessary enzymes.
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PMID:THE CONTROL OF SULPHATE REDUCTION IN BACTERIA. 1434 43

The gram-positive human pathogen Staphylococcus aureus is often isolated with media containing potassium tellurite, to which it has a higher level of resistance than Escherichia coli. The S. aureus cysM gene was isolated in a screen for genes that would increase the level of tellurite resistance of E. coli DH5alpha. The protein encoded by S. aureus cysM is sequentially and functionally homologous to the O-acetylserine (thiol)-lyase B family of cysteine synthase proteins. An S. aureus cysM knockout mutant grows poorly in cysteine-limiting conditions, and analysis of the thiol content in cell extracts showed that the cysM mutant produced significantly less cysteine than wild-type S. aureus SH1000. S. aureus SH1000 cannot use sulfate, sulfite, or sulfonates as the source of sulfur in cysteine biosynthesis, which is explained by the absence of genes required for the uptake and reduction of these compounds in the S. aureus genome. S. aureus SH1000, however, can utilize thiosulfate, sulfide, or glutathione as the sole source of sulfur. Mutation of cysM caused increased sensitivity of S. aureus to tellurite, hydrogen peroxide, acid, and diamide and also significantly reduced the ability of S. aureus to recover from starvation in amino acid- or phosphate-limiting conditions, indicating a role for cysteine in the S. aureus stress response and survival mechanisms.
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PMID:Role of a cysteine synthase in Staphylococcus aureus. 1499 87

Recent studies suggest that apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is another inorganic gaseous mediator in the cardiovascular system. H2S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionin gamma--lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B6) as a cofactor. CBS is the main H2S-producing enzyme in the brain and CSE is involved in H2S formation in the cardiovascular system. H2S induces hypotension in vivo and vasodilation vitro by opening KATP channels in vascular smooth muscle cells. Chronic administration of CSE inhibitor induces arterial hypertension in the rat. In addition, decreased H2S generation has been demonstrated in the vasculature of spontaneously hypertensive rat, in experimental hypertension induced by NO synthase blockade, and in hypoxia-induced pulmonary hypertension, and administration of exogenous H2S donor has significant therapeutic effects in these models. Deficiency of H2S may contribute to atherogenesis in some patients with hyperhomocysteinemia, in whom the metabolism of homocysteine to cysteine and H2S is compromised by vitamin B6 deficiency. Reduced H2S production in the brain was observed in patients with Alzheimer's disease. On the other hand, excess of H2S may lead to mental retardation in patients with Down's syndrome and may be involved in the pathogenesis of hypotension associated with septic shock.
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PMID:[Hydrogen sulfide as a biologically active mediator in the cardiovascular system]. 1528 Jul 98

Human cystathionine beta-synthase (CBS) is a unique pyridoxal-5'-phosphate-dependent enzyme in which heme is also present as a cofactor. Because the function of heme in this enzyme has yet to be elucidated, the study presented herein investigated possible relationships between the chemistry of the heme and the strong pH dependence of CBS activity. This study revealed, via study of a truncation variant, that the catalytic core of the enzyme governs the pH dependence of the activity. The heme moiety was found to play no discernible role in regulating CBS enzyme activity by sensing changes in pH, because the coordination sphere of the heme is not altered by changes in pH over a range of pH 6-9. Instead, pH was found to control the equilibrium amount of ferric and ferrous heme present after reaction of CBS with one-electron reducing agents. A variety of spectroscopic techniques, including resonance Raman, magnetic circular dichroism, and electron paramagnetic resonance, demonstrated that at pH 9 Fe(II) CBS is dominant while at pH 6 Fe(III) CBS is favored. At low pH, Fe(II) CBS forms transiently but reoxidizes by an apparent proton-gated electron-transfer mechanism. Regulation of CBS activity by the iron redox state has been proposed as the role of the heme moiety in this enzyme. Given that the redox behavior of the CBS heme appears to be controlled by pH, interplay of pH and oxidation state effects must occur if CBS activity is redox regulated.
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PMID:The redox behavior of the heme in cystathionine beta-synthase is sensitive to pH. 1554 39

The ability of enzymes to catalyze specific reactions, while excluding others, is central to cellular metabolism. Control of reaction specificity is of particular importance for enzymes that employ catalytically versatile cofactors, of which pyridoxal 5'-phosphate is a prime example. Cystathionine gamma-synthase and cystathionine beta-synthase are the first enzymes in the transsulfuration and reverse transsulfuration pathways, respectively. Each of them occupies branch-point positions in amino acid metabolism and as such are subject to transcriptional and post-translational regulation. Both enzymes catalyze the pyridoxal 5'-phosphate-dependent formation of l-cystathionine; however, their substrate and reaction specificities are distinct. The mechanisms whereby these enzymes control the chemistry of the cofactor are the subject of this review.
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PMID:The enzymology of cystathionine biosynthesis: strategies for the control of substrate and reaction specificity. 1558 75

O-Phosphoserine sulfhydrylase is a new enzyme found in a hyperthermophilic archaeon, Aeropyrum pernix K1. This enzyme catalyzes a novel cysteine synthetic reaction from O-phospho-l-serine and sulfide. The crystal structure of the enzyme was determined at 2.0A resolution using the method of multi-wavelength anomalous dispersion. A monomer consists of three domains, including an N-terminal domain with a new alpha/beta fold. The topology folds of the middle and C-terminal domains were similar to those of the O-acetylserine sulfhydrylase-A from Salmonella typhimurium and the cystathionine beta-synthase from human. The cofactor, pyridoxal 5'-phosphate, is bound in a cleft between the middle and C-terminal domains through a covalent linkage to Lys127. Based on the structure determined, O-phospho-l-serine could be rationally modeled into the active site of the enzyme. An enzyme-substrate complex model and a mutation experiment revealed that Arg297, unique to hyperthermophilic archaea, is one of the most crucial residues for O-phosphoserine sulfhydrylation activity. There are more hydrophobic areas and less electric charges at the dimer interface, compared to the S.typhimurium O-acetylserine sulfhydrylase.
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PMID:Three-dimensional structure of a new enzyme, O-phosphoserine sulfhydrylase, involved in l-cysteine biosynthesis by a hyperthermophilic archaeon, Aeropyrum pernix K1, at 2.0A resolution. 1600 86

Hydrogen sulfide (H2S) at concentrations of about 0.05 to 1 mmol.l(-1) appears to function as a gasotransmitter in vertebrates, analogous to nitric oxide (NO) and carbon monoxide, but the actions of H2S in invertebrate tissue have not been well studied. In this study, we investigated the role of H2S in modulating body wall muscle tone in the marine echiuran worm Urechis caupo (Echiuridae). We first determined that U. caupo body wall homogenates produce H2S upon addition of L-cysteine and pyridoxal-5'-phosphate (PLP), and that the rate is increased by addition of 2-mercaptoethanol, suggesting the presence of an activated L-serine sulfhydrase pathway. We then measured the contractile response of U. caupo body wall circular muscle strips to sodium hydrosulfide (NaHS)--which produces H2S in solution--and the NO donor sodium nitroprusside (SNP), both with and without subsequent application of acetylcholine (ACh). We found that NaHS alone stimulated contraction in muscle strips equivalent to about one-third the force of ACh alone, whereas SNP alone had no effect on muscle tone. However, simultaneous addition of NaHS with SNP elicited a much stronger contraction, reaching more than twice that of ACh alone, which could be increased further by subsequent application of ACh.
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PMID:Sodium nitroprusside potentiates hydrogen-sulfide-induced contractions in body wall muscle from a marine worm. 1611 89

Crude extracts of wild-type Euglena grown in the light (WTL) or in the dark (WTD) and a mutant lacking detectable plastid DNA (W(3)BUL) contain adenosine 5'-phosphosulfate (APS) sulfotransferase. Isotope dilution experiments indicate that adenosine 3'-phosphate 5'-phosphosulfate (PAPS) sulfotransferase is absent.Thiosulfonate reductase, requiring addition of NADH or NADPH but not ferredoxin, and O-acetyl-l-serine sulfhydrylase, the two other enzymes of the bound intermediate pathway of assimilatory sulfate reduction, are also present. Increasing levels of all three enzymes were found in WTL, WTD, and W(3)BUL during logarithmic growth but the various activities were similar at comparable stages of growth in all three types of cell.These results show that the three enzymes are not coded in the chloroplast DNA and are not restricted to Euglena cells having fully developed chloroplasts. Consistent with this, they do not increase during light-induced chloroplast development in resting cells and are found to be enriched in the mitochondrial fraction. Further resolution of this fraction on sucrose gradients shows that the APS sulfotransferase is associated with both the microbody (glyoxysomal) and mitochondrial fractions while the thiosulfonate reductase and O-acetyl-l-serine sulfhydrylase are associated only with the mitochondria. Thus the three known enzymes of the bound pathway of assimilatory sulfate reduction are present in Euglena mitochondria.Although the activity of the entire bound pathway (APS to cysteine) is low in extracts, addition of dithiothreitol which releases free sulfite from the product of the APS sulfotransferase reaction, causes an increase in reduction activity indicating that a sulfite reductase is also present. It remains to be shown which reducing system is the significant one in vivo in Euglena.
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PMID:Studies of sulfate utilization of algae: 15. Enzymes of assimilatory sulfate reduction in euglena and their cellular localization. 1665 97


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