Structure and Function of Subtilisin BPN’ as Studied Through Crystallographic Studies on a Series of its Complexes with Genetically Engineered Proteinaceous Inhibitor SSI

Abstract

Streptomyces subtilisin inhibitor (SSI) is one of the few well-characterized microbial proteinase inhibitors and is a stable dimer (I₂) composed of two identical subunits, each of molecular weight 1 1,500¹. It strongly inhibits a microbial serine proteinase, subtilisin BPN’ (E), forming an E₂I₂ complex of molecular weight 79,000. There are many grounds for believing that the structures of the complexes of serine proteinases with their proteinaceous inhibitors are only subtly different from those of the complexes with true substrates. A proteinaceous inhibitor bound on the target enzyme can be regarded as the substrate trapped in a potential energy minimum. The structure and function of the SSI-subtilisin system have been extensively studied as reviewed in a monograph on SSI². We solved the crystal structures of free SSI^3,4 and SSI-subtilisin complex^5,6 both of which are now refined at 1.9 Å resolution.