| http://purl.uniprot.org/citations/28696262 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28696262 | http://www.w3.org/2000/01/rdf-schema#comment | "There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist d-serine. Reported correlation of d-serine levels with disorders including Alzheimer's disease, ALS, and ischemic brain damage (elevated d-serine) and schizophrenia (reduced d-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser84, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of l-serine over the normally preferred l-serine-O-sulfate (∼1200-fold change in kcat/Km ratios) and l (l-THA; ∼5000-fold change in kcat/Km ratios) alternative substrates. On the other hand, the S84T (which performs l-Ser racemization activity), S84A (good kcat but high Km for l-THA elimination), and S84N mutants (nearly WT efficiency for l-Ser elimination) displayed intermediate activity, all showing a preference for the anionic substrates, but generally attenuated compared with the native enzyme. Inhibition studies with l-erythro-β-hydroxyaspartate follow this trend, with both WT serine racemase and the S84N mutant being competitively inhibited, with Ki = 31 ± 1.5 μm and 1.5 ± 0.1 mm, respectively, and the S84D being inert to inhibition. Computational modeling pointed to a key role for residue Arg-135 in binding and properly positioning the l-THA and l-serine-O-sulfate substrates and the l-erythro-β-hydroxyaspartate inhibitor. Examination of available sequence data suggests that Arg-135 may have originated for l-THA-like β-elimination function in earlier evolutionary variants, and examination of available structural data suggests that a Ser84-H2O-Lys114 hydrogen-bonding network in human serine racemase lowers the pKa of the Ser84re-face base."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m117.777904"xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/author | "Nelson D.L."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/author | "Graham D.L."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/author | "Berkowitz D.B."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/author | "Applegate G.A."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/author | "Beio M.L."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/pages | "13986-14002"xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/title | "Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for beta-elimination function."xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://purl.uniprot.org/core/volume | "292"xsd:string |
| http://purl.uniprot.org/citations/28696262 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28696262 |
| http://purl.uniprot.org/citations/28696262 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28696262 |
| http://purl.uniprot.org/uniprot/#_Q8N3F4-mappedCitation-28696262 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/#_Q3ZK31-mappedCitation-28696262 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/#_Q53G11-mappedCitation-28696262 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/#_Q9GZT4-mappedCitation-28696262 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/Q9GZT4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/Q53G11 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/Q3ZK31 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28696262 |
| http://purl.uniprot.org/uniprot/Q8N3F4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28696262 |