X-ray structure of the uncomplexed anti-tumor antibody BR96 and comparison with its antigen-bound form.

The X-ray structure of the uncomplexed human chimeric Fab' of the anti-tumor antibody BR96 has been determined at 2.6 A resolution. The structure has been compared with Lewis Y antigen-complexed structures of BR96 which were determined previously. The comparison reveals segmental motions and/or conformational rearrangements of three CDR loops (L1, L3, and H2), whereas CDR H3 does not undergo changes upon complexation despite its significant main-chain contacts to the carbohydrate antigen. In light of the uncomplexed chimeric Fab' structure reported here, the previously observed high mobility of the CL:CH1 domains of the complexed chimeric BR96 Fab is rationalized as a "swinging" motion approximately about the axis of the elbow bend.