Farnesyltransferase--new insights into the zinc-coordination sphere paradigm: evidence for a carboxylate-shift mechanism.

ABSTRACT: Despite the enormous interest that has been devoted to the study of farnesyltransferase, many questions concerning its catalytic mechanism remain unanswered. In particular, several doubts exist on the structure of the active-site zinc coordination sphere, more precisely on the nature of the fourth ligand, which is displaced during the catalytic reaction by a peptide thiolate. From available crystallographic structures, and mainly from x-ray absorption fine structure data, two possible alternatives emerge: a tightly zinc-bound water molecule or an almost symmetrical bidentate aspartate residue (Asp-297beta). In this study, high-level theoretical calculations, with different-sized active site models, were used to elucidate this aspect. Our results demonstrate that both coordination alternati

SUBMITTER: Sousa SF 

PROVIDER: S-EPMC1305025 | biostudies-literature | 2005 Jan

REPOSITORIES: biostudies-literature