Elucidation of the proton transport mechanism in human carbonic anhydrase II.

ABSTRACT: Human carbonic anhydrase II (HCA II) is one of the fastest known enzymes, which utilizes a rate-limiting proton transport (PT) step in its enzymatic reaction. To evaluate the PT event at an atomistic level, the multistate empirical valence bond (MS-EVB) method has been utilized in this work. It is observed that the PT event in HCA II exploits a transient active site water cluster to transport the excess proton between the catalytic zinc-bound water/hydroxide and the proton shuttling residue, His64. This PT event is found to be dependent on the enzyme's ability to form and stabilize the active site water cluster in addition to its ability to orient His64 in a favorable conformation. Evaluation of the PT free energy barrier for different orientations of His64 reveals this residue's vital rol

SUBMITTER: Maupin CM 

PROVIDER: S-EPMC2774804 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature