Title
Understanding nicotinamide dinucleotide cofactor and substrate specificity in class I flavoprotein disulfide oxidoreductases : crystallographic analysis of a glutathione amide reductase Understanding nicotinamide dinucleotide cofactor and substrate specificity in class I flavoprotein disulfide oxidoreductases : crystallographic analysis of a glutathione amide reductase
Author
Faculty/Department
Faculty of Sciences. Biology
Publication type
article
Publication
London ,
Subject
Biology
Source (journal)
Journal of molecular biology. - London
Volume/pages
374(2007) :4 , p. 883-889
ISSN
0022-2836
ISI
000251700900003
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Glutathione reductase (GR) plays a vital role in maintaining the antioxidant levels of the cytoplasm by catalyzing the reduction of glutathione disulfide to reduced glutathione, thereby using NADPH and flavin adenine dinucleotide as cofactors. Chromatiaceae have evolved an unusual homolog that prefers both a modified substrate (glutathione amide disulfide [GASSAG]) and a different cofactor (NADH). Herein, we present the crystal structure of the Chromatium gracile glutathione amide reductase (GAR) both alone and in complex with NAD+. An altered charge distribution in the GASSAG binding pocket explains the difference in substrate specificity. The NADH binding pocket of GAR differs from that of wild-type GR as well as that of a low active GR that was engineered to mimic NADH binding. Based on the GAR structure, we propose two attractive rationales for producing an efficient GR enzyme with NADH specificity.
E-info
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