3L6C
X-ray crystal structure of rat serine racemase in complex with malonate a potent inhibitor
Summary for 3L6C
| Entry DOI | 10.2210/pdb3l6c/pdb |
| Related | 3L6B 3L6R |
| Descriptor | Serine racemase, PYRIDOXAL-5'-PHOSPHATE, MANGANESE (II) ION, ... (5 entities in total) |
| Functional Keywords | pyridoxal phosphate, plp, serine racemase, isomerase |
| Biological source | Rattus norvegicus (rat) |
| Total number of polymer chains | 2 |
| Total formula weight | 73967.66 |
| Authors | Smith, M.A.,Mack, V.,Ebneth, A.,Moraes, I.,Felicetti, B.,Wood, M.,Schonfeld, D.,Mather, O.,Cesura, A.,Barker, J. (deposition date: 2009-12-23, release date: 2010-01-26, Last modification date: 2024-04-03) |
| Primary citation | Smith, M.A.,Mack, V.,Ebneth, A.,Moraes, I.,Felicetti, B.,Wood, M.,Schonfeld, D.,Mather, O.,Cesura, A.,Barker, J. The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding. J.Biol.Chem., 285:12873-12881, 2010 Cited by PubMed Abstract: 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. PubMed: 20106978DOI: 10.1074/jbc.M109.050062 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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