REDETERMINATION AND REFINEMENT OF THE COMPLEX OF BENZYLSUCCINIC ACID WITH THERMOLYSIN AND ITS RELATION TO THE COMPLEX WITH CARBOXYPEPTIDASE-A

The complex of benzylsuccinic acid with thermolysin has been redetermi ned at 1.7-Angstrom resolution and refined to a crystallographic resid ual of 15.7%. In contrast to the prior study, which was to 2.3-Angstro m resolution, and with-out the benefit of refinement (Bolognesi, M. C. and Matthews, B. W. (1979) J. Biol. Chem. 254, 634-639), the present analysis shows that it is the D- rather than the L-isomer of benzylsuc cinic acid that binds. The stereochemistry of the zinc-carboxylate int eraction is now seen to be syn, as is also observed in all known zinc- carboxylate complexes of both thermolysin and carboxypeptidase A. The mode of binding of the beta-carboxylate resembles the presumed geometr y of the tetrahedral transition state and, as such, is consistent with the commonly accepted mechanism of action of thermolysin and of carbo xypeptidase A.