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X-Ray Analysis of a Difluorostatone Renin Inhibitor Bound as the Tetrahedral Hydrate to the Aspartic Protease Endothiapepsin

  • Dennis J. Hoover
  • Balusubramanian Veerapandian
  • Jon B. Cooper
  • David B. Damon
  • Beryl W. Dominy
  • Robert L. Rosati
  • Tom L. Blundell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)

Abstract

In this study we report the X-ray analysis of a complex between the aspartic protease endothiapepsin (EC 3.4.23.6) 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

Keywords

Aspartic Protease Renin Inhibitor Hydroxyl Oxygen Tetrahedral Intermediate Conserve Water Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Dennis J. Hoover
    • 1
  • Balusubramanian Veerapandian
    • 2
  • Jon B. Cooper
    • 2
  • David B. Damon
    • 1
  • Beryl W. Dominy
    • 1
  • Robert L. Rosati
    • 1
  • Tom L. Blundell
    • 2
  1. 1.Department of Medicinal Chemistry, Central Research DivisionPfizer, IncGrotonUSA
  2. 2.Laboratory of Molecular Biology, Department of CrystallographyBirkbeck CollegeLondonUK

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