Structural and kinetic study of the extended active site for proton transfer in human carbonic anhydrase II.

ABSTRACT: The catalysis of CO(2) hydration by human carbonic anhydrase II (HCA II) is limited in maximal velocity by proton transfer from a zinc-bound water molecule to the proton shuttle His64. This proton transfer occurs along a hydrogen-bonded water network, leading to the proton shuttle residue His64, which in turn transfers the proton to bulk solvent. The side chain of His64 occupies two conformations in wild-type HCA II, pointing inward toward the zinc or outward toward bulk solvent. Previously, several studies have examined the roles of residues of the active site cavity that interact with the solvent-mediated hydrogen-bonded network between His64 and the zinc-bound water. Here these studies are extended to examine the effects on proton transfer by mutation at Lys170 (to Ala, Asp, Glu, and Hi

SUBMITTER: Domsic JF 

PROVIDER: S-EPMC2925223 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature