3L6B

X-ray crystal structure of human serine racemase in complex with malonate a potent inhibitor

3L6B の概要

• エントリーDOI: 10.2210/pdb3l6b/pdb
• 関連するPDBエントリー: 3L6C 3L6R
• 分子名称: Serine racemase, PYRIDOXAL-5'-PHOSPHATE, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: pyridoxal phosphate, plp, serine racemase, isomerase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37859.99

構造登録者

Smith, M.A.,Barker, J.,Mack, V.,Ebneth, A.,Moraes, I.,Felicetti, B.,Cesura, A. (登録日: 2009-12-23, 公開日: 2010-01-26, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.5 Å)