RGD Reference Report - The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding. - Rat Genome Database

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The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding.

Authors: Smith, MA  Mack, V  Ebneth, A  Moraes, I  Felicetti, B  Wood, M  Schonfeld, D  Mather, O  Cesura, A  Barker, J 
Citation: Smith MA, etal., J Biol Chem. 2010 Apr 23;285(17):12873-81. doi: 10.1074/jbc.M109.050062. Epub 2010 Jan 27.
RGD ID: 8554326
Pubmed: (View Article at PubMed) PMID:20106978
DOI: Full-text: DOI:10.1074/jbc.M109.050062

Serine racemase is responsible for the synthesis of D-serine, an endogenous co-agonist for N-methyl-D-aspartate receptor-type glutamate receptors (NMDARs). This pyridoxal 5'-phosphate-dependent enzyme is involved both in the reversible conversion of L- to D-serine and serine catabolism by alpha,beta-elimination of water, thereby regulating D-serine levels. Because D-serine affects NMDAR signaling throughout the brain, serine racemase is a promising target for the treatment of disorders related to NMDAR dysfunction. To provide a molecular basis for rational drug design the x-ray crystal structures of human and rat serine racemase were determined at 1.5- and 2.1-A resolution, respectively, and in the presence and absence of the orthosteric inhibitor malonate. The structures revealed a fold typical of beta-family pyridoxal 5'-phosphate enzymes, with both a large domain and a flexible small domain associated into a symmetric dimer, and indicated a ligand-induced rearrangement of the small domain that organizes the active site for specific turnover of the substrate.



Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Srr  (serine racemase)


Additional Information