3-DIMENSIONAL STRUCTURE OF THE COMPLEX OF THE RHIZOPUS-CHINENSIS CARBOXYL PROTEINASE AND PEPSTATIN AT 2.5-A RESOLUTION

An X-ray diffraction analysis was carried out at 2.5-.ANG. resolution of the 3-dimensional structure of the R. chinensis carboxyl proteinase complexed with pepstatin. The resulting model of the complex supports the hypothesis (Marciniszyn, et al. 1976) that statine (3-hydroxy-4-amino-6-methylheptanoic acid) appraoches an analog of the transition state for catalysis. The way in which pepstatin binds to the enzyme can be extended to provide a model of substrate binding and a model of the transition-state complex. This has led to a proposed mechanism of action based on general acid-base catalysis with no covalent intermediates. These predictions are in general agreement with kinetic studies using several carboxyl proteinases, which together with their sequence homology and their common 3-dimensional structures suggest that this mechanism can be extrapolated to all carboxyl proteinases.