L-butaneboronic acid binding to Aeromonas proteolytica aminopeptidase:: A case of arrested development

Hydrolases containing two metal ions connected by a bridging ligand catalyze reactions important in carcinogensis, tissue repair, post-translational modification, control and regulation of biochemical pathways, and protein degradation. The aminopeptidase from Aeromonas proteolytica serves as a paradigm for the study of such bridged bimetallic proteases since its three-dimensional structure is known to very high resolution and its catalytic reaction is amenable to spectroscopic examination. Herein, we report, the X-ray crystal structure at 1.9 Angstrom resolution of AAP complexed with 1-butaneboronic acid (BuBA). This structure suggests that this complex represents a snapshot of the proteolytic reaction in an arrested form between the Michaelis complex and the transition state. Comparison of-the structure with spectroscopic and other data allows us to conclude that the apparently structurally symmetrical dizinc site is actually asymmetric: electrostatically.