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 redetermined at 1.7-A resolution and refined to a crystallographic residual of 15.7%. In contrast to the prior study, which was to 2.3-A resolution, and without 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 benzylsuccinic acid that binds. The stereochemistry of the zinc-carboxylate interaction 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 geometry of the tetrahedral transition state and, as such, is consistent with the commonly accepted mechanism of action of thermolysin and of carboxypeptidase A.
Institute of Molecular Biology, University of Oregon, Eugene 97403.
A C
AC
Hausrath
B W
BW
Matthews
D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry*; D043422:Carboxypeptidases A; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008667:Metalloproteins / Q000737:chemistry; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013386:Succinates / Q000737:chemistry*; D013820:Thermolysin / Q000737:chemistry*; D015032:Zinc
D008667:Metalloproteins; D013386:Succinates; C000249:benzylsuccinic acid; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D013820:Thermolysin; D015032:Zinc