2f2k
From Proteopedia
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Aldose reductase tertiary complex with NADPH and DEG
Overview
Aldose reductase (AR) is a monomeric NADPH-dependent oxidoreductase that, catalyzes the reduction of aldehydes, ketones, and aldo-sugars. AR has, been linked to the development of hyperglycemic injury and is a clinical, target for the treatment of secondary diabetic complications. In addition, to reducing glucose, AR is key regulator of cell signaling through it's, reduction of aldehydes derived from lipoproteins and membrane, phospholipids. AR catalyzes the reduction of glutathione conjugates of, unsaturated aldehydes with higher catalytic efficiency than free, aldehydes. The X-ray structure of human AR holoenzyme in complex with the, glutathione analogue S-(1,2-dicarboxyethyl) glutathione (DCEG) was, determined at a resolution of 1.94 A. The distal carboxylate group of, DCEG's dicarboxyethyl moiety interacted with the conserved AR anion, binding site residues Tyr48, His110, and Trp111. The bound DCEG's, glutathione backbone adopted the low-energy Y-shape form. The C-terminal, carboxylate of DCEG glutathione's glycine formed hydrogen bonds to Leu301, and Ser302, while the remaining interactions between DCEG and AR were, hydrophobic, permitting significant flexibility of the AR and glutathione, (GS) analogue interaction. The observed conformation and interactions of, DCEG with AR were consistent with our previously published molecular, dynamics model of glutathionyl-propanal binding to AR. The current, structure identifies major interactions of glutathione conjugates with the, AR active-site residues.
About this Structure
2F2K is a Single protein structure of sequence from Homo sapiens with NDP and TGG as ligands. Active as Aldehyde reductase, with EC number 1.1.1.21 Full crystallographic information is available from OCA.
Reference
Structure of a glutathione conjugate bound to the active site of aldose reductase., Singh R, White MA, Ramana KV, Petrash JM, Watowich SJ, Bhatnagar A, Srivastava SK, Proteins. 2006 Jul 1;64(1):101-10. PMID:16639747
Page seeded by OCA on Mon Nov 12 21:59:01 2007
