Structure of human glycolate oxidase in complex with the inhibitor 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole.
Acta Crystallogr Sect F Struct Biol Cryst Commun
; 65(Pt 12): 1246-53, 2009 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-20054120
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tiadiazoles
/
Oxidorreductasas de Alcohol
Límite:
Humans
Idioma:
En
Revista:
Acta Crystallogr Sect F Struct Biol Cryst Commun
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suecia