Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics.

ABSTRACT: Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used a covalent capture selection strategy to identify biocatalysts from within a human semisynthetic antibody variable fragment library that uses a nucleophilic mechanism. Specific phosphonylation at a single tyrosine within the variable light-chain framework was confirmed in a recombinant IgG construct. High-resolution crystallographic structures of unmodified and phosphonylated Fabs display a 15-Å-deep two-chamber cavity at the interface of variable light (V(L)) and variable heavy (V(H)) fragments having a nucleophilic tyrosine at the base of the site. The depth and structure of the pocket are atypical of antibodies in general but can be compa

SUBMITTER: Smirnov I 

PROVIDER: S-EPMC3179052 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature