2W0U

CRYSTAL STRUCTURE OF HUMAN GLYCOLATE OXIDASE IN COMPLEX WITH THE INHIBITOR 5-[(4-CHLOROPHENYL)SULFANYL]- 1,2,3-THIADIAZOLE-4-CARBOXYLATE.

2W0U の概要

• エントリーDOI: 10.2210/pdb2w0u/pdb
• 分子名称: HYDROXYACID OXIDASE 1, 5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole-4-carboxylate, FLAVIN MONONUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: flavoprotein, glycolate pathway, hydroxyacid oxidase 1, oxidoreductase, peroxisome, inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 166817.28

構造登録者

Bourhis, J.M.,Lindqvist, Y. (登録日: 2008-10-10, 公開日: 2009-11-10, 最終更新日: 2023-12-13)

主引用文献

Bourhis, J.M.,Vignaud, C.,Pietrancosta, N.,Gueritte, F.,Guenard, D.,Lederer, F.,Lindqvist, Y.
Structure of Human Glycolate Oxidase in Complex with the Inhibitor 4-Carboxy-5-[(4-Chlorophenyl)Sulfanyl]-1,2,3-Thiadiazole.
Acta Crystallogr.,Sect.F, 65:1246-, 2009

PubMed Abstract: Glycolate oxidase, a peroxisomal flavoenzyme, generates glyoxylate at the expense of oxygen. When the normal metabolism of glyoxylate is impaired by the mutations that are responsible for the genetic diseases hyperoxaluria types 1 and 2, glyoxylate yields oxalate, which forms insoluble calcium deposits, particularly in the kidneys. Glycolate oxidase could thus be an interesting therapeutic target. The crystal structure of human glycolate oxidase (hGOX) in complex with 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole (CCPST) has been determined at 2.8 A resolution. The inhibitor heteroatoms interact with five active-site residues that have been implicated in catalysis in homologous flavodehydrogenases of L-2-hydroxy acids. In addition, the chlorophenyl substituent is surrounded by nonconserved hydrophobic residues. The present study highlights the role of mobility in ligand binding by glycolate oxidase. In addition, it pinpoints several structural differences between members of the highly conserved family of flavodehydrogenases of L-2-hydroxy acids.

PubMed: 20054120
DOI: 10.1107/S1744309109041670

実験手法

X-RAY DIFFRACTION (2.84 Å)