X-RAY STRUCTURE OF THE UNCOMPLEXED ANTITUMOR 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 Angstrom resolution. T he structure has been compared with Lewis Y antigen-complexed structur es of BR96 which were determined previously. The comparison reveals se gmental motions and/or conformational rearrangements of three CDR loop s (L1, L3, and H2), whereas CDR H3 does not undergo changes upon compl exation despite its significant main-chain contacts to the carbohydrat e antigen. In light of the uncomplexed chimeric Fab' structure reporte d here, the previously observed high mobility of the CL:CH1 domains of the complexed chimeric BR96 Fab is rationalized as a ''swinging'' mot ion approximately about the axis of the elbow bend. (C) 1996 Academic Press Limited