An understanding of the molecular basis of action, or mechanism, of proteolytic enzymes is a long-term objective of biochemical investigation, realization of which would have multiple benefits with regard to medical problems associated with protein metabolism. For metalloproteases, new substrates are being developed to aid in assay for proteolytic activity. Novel inhibitors and inactivators are being designed as probes of mechanism, and as potential leads to biomedically efficacious agents. Independent developments in structural biochemistry (crystallography) have created fresh opportunities by identifying new subcategories of metalloproteases, specifically dual-metal ion aminopeptidases and astacin- type proteases, for which kinetic investigations being undertaken are greatly needed for clarification of mechanism. Materials developed in this project should have applicability to a range of current challenges in protein chemistry, including hormone processing, collagen degradation, and invasive cancer.
| Mock, W L; Cheng, H (2000) Principles of hydroxamate inhibition of metalloproteases: carboxypeptidase A. Biochemistry 39:13945-52 |
| Mock, W L; Wang, L (1999) Synergistic inhibition of carboxypeptidase A by zinc ion and imidazole. Biochem Biophys Res Commun 257:239-43 |
| Mock, W L; Xu, D (1999) Catalytic activity of carboxypeptidase B and of carboxypeptidase Y with anisylazoformyl substrates. Bioorg Med Chem Lett 9:187-92 |
| Mock, W L; Yao, J (1997) Kinetic characterization of the serralysins: a divergent catalytic mechanism pertaining to astacin-type metalloproteases. Biochemistry 36:4949-58 |
| Mock, W L; Liu, Y; Stanford, D J (1996) Arazoformyl peptide surrogates as spectrophotometric kinetic assay substrates for carboxypeptidase A. Anal Biochem 239:218-22 |
| Mock, W L; Stanford, D J (1996) Arazoformyl dipeptide substrates for thermolysin. Confirmation of a reverse protonation catalytic mechanism. Biochemistry 35:7369-77 |
