3L6R

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

Summary for 3L6R

• Entry DOI: 10.2210/pdb3l6r/pdb
• Related: 3HMK 3L6B 3L6C
• Descriptor: Serine racemase, MALONATE ION, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: pyridoxal phosphate, plp, serine racemase, isomerase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 38075.43

Authors

Smith, M.A.,Mack, V.,Ebneth, A.,Cesura, A.,Felicetti, B.,Barker, J. (deposition date: 2009-12-24, release date: 2010-01-26, Last modification date: 2021-11-10)

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

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: 20106978
DOI: 10.1074/jbc.M109.050062

Experimental method

X-RAY DIFFRACTION (1.7 Å)