Origins of enhanced proton transport in the Y7F mutant of human carbonic anhydrase II.

ABSTRACT: Human carbonic anhydrase II (HCA II), among the fastest enzymes known, catalyzes the reversible hydration of CO 2 to HCO 3 (-). The rate-limiting step of this reaction is believed to be the formation of an intramolecular water wire and transfer of a proton across the active site cavity from a zinc-bound solvent to a proton shuttling residue (His64). X-ray crystallographic studies have shown this intramolecular water wire to be directly stabilized through hydrogen bonds via a small well-defined set of amino acids, namely, Tyr7, Asn62, Asn67, Thr199, and Thr200. Furthermore, X-ray crystallographic and kinetic studies have shown that the mutation of tyrosine 7 to phenylalanine, Y7F HCA II, has the effect of increasing the proton transfer rate by 7-fold in the dehydration direction of the enzy

SUBMITTER: Maupin CM 

PROVIDER: S-EPMC2562593 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature