Analysis of crystal structures of aspartic proteinases: On the role of amino acid residues adjacent to the catalytic site of pepsin‐like enzymes
- 31 December 2001
- journal article
- Published by Wiley in Protein Science
- Vol. 10 (12), 2439-2450
- https://doi.org/10.1110/ps.25801
Abstract
To elucidate the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes, we analyzed and compared the crystal structures of these enzymes, their complexes with inhibitors, and zymogens in the active site area (a total of 82 structures). In addition to the water molecule (W1) located between the active carboxyls and playing a role of the nucleophile during catalytic reaction, another water molecule (W2) at the vicinity of the active groups was found to be completely conserved. This water molecule plays an essential role in formation of a chain of hydrogen-bonded residues between the active site flap and the active carboxyls on ligand binding. These data suggest a new approach to understanding the role of residues around the catalytic site, which can assist the development of the catalytic reaction. The influence of groups adjacent to the active carboxyls is manifested by pepsin activity at pH 1.0. Some features of pepsin-like enzymes and their mutants are discussed in the framework of the approach.Keywords
This publication has 84 references indexed in Scilit:
- The Protein Data BankNucleic Acids Research, 2000
- Macrocyclic Inhibitors of Penicillopepsin. 2. X-ray Crystallographic Analyses of Penicillopepsin Complexed with a P3−P1 Macrocyclic Peptidyl Inhibitor and with Its Two Acyclic AnaloguesJournal of the American Chemical Society, 1998
- Crystallographic Studies on the Binding Modes of P2-P3 Butanediamide Renin InhibitorsPublished by Elsevier BV ,1995
- High Resolution Crystal Structures of Recombinant Human Renin in Complex with Polyhydroxymonoamide InhibitorsJournal of Molecular Biology, 1995
- X-ray Analysis at 2·0 Å Resolution of Mouse Submaxillary Renin Complexed with a Decapeptide Inhibitor CH-66, Based on the 4-16 Fragment of Rat AngiotensinogenJournal of Molecular Biology, 1994
- Synthesis and crystallographic analysis of two rhizopuspepsin inhibitor complexesBiochemistry, 1992
- Refined structure of porcine pepsinogen at 1·8 Å resolutionJournal of Molecular Biology, 1991
- Molecular and crystal structures of monoclinic porcine pepsin refined at 1.8A˚resolutionJournal of Molecular Biology, 1990
- Structure and refinement of penicillopepsin at 1.8 Å resolutionJournal of Molecular Biology, 1983
- The protein data bank: A computer-based archival file for macromolecular structuresJournal of Molecular Biology, 1977