Structure of an engineered, metal-actuated switch in trypsin.

The X-ray crystal structure of the copper complex of the rat trypsin mutant Arg96 to His96 (trypsin R96H) has been determined in order to ascertain the nature of the engineered metal-binding site and to understand the structural basis for the metal-induced enzymatic inhibition. In the structure, the catalytically essential His57 residue is reoriented out of the active-site pocket and forms a chelating, metal-binding site with residue His96. The copper is bound to the Ne2 atoms of both histidine residues with Cu-Ne2=2.2 A and Ne2-Cu-Ne2=89 o