Proton transfer pathways in the mutant His-64-Ala of human carbonic anhydrase II

被引:16
作者
Roy, Arijit [1 ]
Taraphder, Srabani [1 ]
机构
[1] Indian Inst Technol, Dept Chem, Kharagpur 721302, W Bengal, India
关键词
proton transfer pathways; mutant His-64-Ala; human carbonic anhydrase II; 4-methylimidazole;
D O I
10.1002/bip.20516
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 H. 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 it? 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. (c) 2006 Wiley Periodicals, Inc.
引用
收藏
页码:623 / 630
页数:8
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