Proton transfer pathways in the mutant His-64-Ala of human carbonic anhydrase II.
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.
Roy
Arijit
A
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
Taraphder
Srabani
S
D019943:Amino Acid Substitution; D001704:Biopolymers / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020134:Catalytic Domain; D006801:Humans; D007093:Imidazoles; D066298:In Vitro Techniques; D008958:Models, Molecular; D009154:Mutation; D011522:Protons; D014867:Water / Q000737:chemistry
D001704:Biopolymers; D007093:Imidazoles; D011522:Protons; D014867:Water; D024402:Carbonic Anhydrase II; C023439:4-methylimidazole