Molecular mechanism of enantioselective proton transfer to carbon in catalytic antibody 14D9.

ABSTRACT: Catalytic antibody 14D9 catalyzes the enantioselective protonation of prochiral enol ethers with high enantioselectivity (>99% ee) and a practical turnover (k(cat) = 0.4 s(-1)), allowing for preparative scale applications. This antibody represents one of the rare examples of catalytic antibodies promoting acid-catalyzed processes. Antibody 14D9 was cloned and expressed as a chimeric Fab fragment in Escherichia coli. Crystal structures of Fab 14D9 as apo form and of its close analog 19C9 in complex with the transition state analog were determined at 2.8-A resolution. A series of site-directed mutagenesis experiments was carried out to probe the role of individual active-site amino acids. Proton transfer to carbon is catalyzed by a hydrogen bond network formed by the side chains of Asp(H101)

SUBMITTER: Zheng L 

PROVIDER: S-EPMC376184 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature