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Proton transfer pathways in the mutant His‐64–Ala of human carbonic anhydrase II
Author(s) -
Roy Arijit,
Taraphder Srabani
Publication year - 2006
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20516
Subject(s) - carbonic anhydrase ii , chemistry , carbonic anhydrase , proton , mutant , molecule , catalysis , preprint , proton transport , enzyme , crystallography , stereochemistry , biophysics , biochemistry , organic chemistry , membrane , physics , quantum mechanics , biology , world wide web , computer science , gene
We have investigated the possible proton transfer pathways from the surface of the protein to the zinc‐bound water molecule in the mutant His‐64–Ala of human carbonic anhydrase II. Starting with an input of known crystallographic structures of the mutant, we model the proton pathways as hydrogen‐bonded networks of proton conducting groups and bound solvent molecules. No proton path is detected in the mutant, in close agreement with the experimental observation of a 20‐fold decrease in its catalytic efficiency compared to the wild‐type enzyme. We also investigate in detail changes in hydration structure at the active site of the mutant and the resulting proton paths in the presence of an exogenous proton donor 4‐methylimidazole (4‐MI). The proton transfer pathways thus detected are correlated to the observed chemical rescue of catalytic activity by 4‐MI. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 623–630, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com