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

Hydrolases containing two metal ions connected by a bridging ligand catalyz e reactions important in carcinogensis, tissue repair, post-translational m odification, control and regulation of biochemical pathways, and protein de gradation. The aminopeptidase from Aeromonas proteolytica serves as a parad igm for the study of such bridged bimetallic proteases since its three-dime nsional structure is known to very high resolution and its catalytic reacti on is amenable to spectroscopic examination. Herein, we report, the X-ray c rystal structure at 1.9 Angstrom resolution of AAP complexed with 1-butaneb oronic acid (BuBA). This structure suggests that this complex represents a snapshot of the proteolytic reaction in an arrested form between the Michae lis complex and the transition state. Comparison of-the structure with spec troscopic and other data allows us to conclude that the apparently structur ally symmetrical dizinc site is actually asymmetric: electrostatically.