Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody.

ABSTRACT: The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was found that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared

SUBMITTER: Ponomarenko N 

PROVIDER: S-EPMC3949517 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature