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http://purl.uniprot.org/citations/33249721http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33249721http://www.w3.org/2000/01/rdf-schema#comment"Human serine racemase (hSR) catalyzes the biosynthesis of D-serine, an obligatory co-agonist of the NMDA receptors. It was previously found that the reversible S-nitrosylation of Cys113 reduces hSR activity. Here, we show by site-directed mutagenesis, fluorescence spectroscopy, mass spectrometry, and molecular dynamics that S-nitrosylation stabilizes an open, less-active conformation of the enzyme. The reaction of hSR with either NO or nitroso donors is conformation-dependent and occurs only in the conformation stabilized by the allosteric effector ATP, in which the ε-amino group of Lys114 acts as a base toward the thiol group of Cys113. In the closed conformation stabilized by glycine-an active-site ligand of hSR-the side chain of Lys114 moves away from that of Cys113, while the carboxyl side-chain group of Asp318 moves significantly closer, increasing the thiol pKa and preventing the reaction. We conclude that ATP binding, glycine binding, and S-nitrosylation constitute a three-way regulation mechanism for the tight control of hSR activity. We also show that Cys113 undergoes H2 O2 -mediated oxidation, with loss of enzyme activity, a reaction also dependent on hSR conformation."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.org/dc/terms/identifier"doi:10.1111/febs.15645"xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Bruno S."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Mozzarelli A."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Marchesani F."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Bettati S."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Campanini B."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Michielon A."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Faggiano S."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Gianquinto E."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Spyrakis F."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/author"Autiero I."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/name"FEBS J"xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/pages"3034-3054"xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/title"The allosteric interplay between S-nitrosylation and glycine binding controls the activity of human serine racemase."xsd:string
http://purl.uniprot.org/citations/33249721http://purl.uniprot.org/core/volume"288"xsd:string
http://purl.uniprot.org/citations/33249721http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33249721
http://purl.uniprot.org/citations/33249721http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33249721
http://purl.uniprot.org/uniprot/#_Q8N3F4-mappedCitation-33249721http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33249721
http://purl.uniprot.org/uniprot/#_Q3ZK31-mappedCitation-33249721http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33249721
http://purl.uniprot.org/uniprot/#_Q53G11-mappedCitation-33249721http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33249721
http://purl.uniprot.org/uniprot/#_Q9GZT4-mappedCitation-33249721http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33249721
http://purl.uniprot.org/uniprot/Q9GZT4http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33249721