X-Ray Analysis of a Difluorostatone Renin Inhibitor Bound as the Tetrahedral Hydrate to the Aspartic Protease Endothiapepsin
In this study we report the X-ray analysis of a complex between the aspartic protease endothiapepsin (EC 220.127.116.11) and an inhibitor bound as a carbonyl hydrate (gem-diol) to the catalytic aspartates of this enzyme, in a manner closely resembling the putative tetrahedral intermediate in proteolytic cleavage of the peptide bond.1 This study was undertaken in order to obtain a closer model of the interactions stabilizing this intermediate than those used in previous analyses, which were based on X-ray crystallographic data obtained from inhibitors lacking one or both of the hydroxyl residues of this species.2,3
KeywordsAspartic Protease Renin Inhibitor Hydroxyl Oxygen Tetrahedral Intermediate Conserve Water Molecule
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