Sherwin Wilk, PhD

Proteolytic enzymes
Our laboratory is involved in research on the properties and functional significance of proteolytic enzymes. In recent years it has become clear that proteolytic enzymes mediate many important cellular processes including: the activation and inactivation of regulatory molecules and transcription factors, the biosynthesis and inactivation of neuropeptides, and apoptosis. The therapeutic significance of proteolytic enzymes is seen by the use of their inhibitors as drugs. This is exemplified by the ever-increasing application of angiotensin converting enzyme inhibitors in the treatment of cardiovascular diseases and the introduction of HIV protease inhibitors for the treatment of AIDS. The design and synthesis of inhibitors of proteolytic enzymes is one of the major aims of our research program.

Proteasome
The proteasome (multicatalytic proteinase complex), first isolated and characterized in our laboratory almost twenty years ago, is a high molecular mass proteolytic molecule found in relatively high concentrations in the cytosol and nucleus of all eukaryotic cells. The explosive growth of research on the proteasome is accounted for by evidence of its essential role in many fundamental cellular processes. Basic questions about the relationship of the structure of the proteasome to its function and its mechanism of regulation in vivo, remain unanswered. We are studying the mechanism of activation of the proteasome by several endogenous nuclear activator proteins and the physiological significance of endogenous activators.

Aspartyl Aminopeptidase
We have purified, characterized, cloned and expressed a new acidic amino acid preferring aminopeptidase. One of its important biological substrates is the vasoactive peptide angiotensin. This enzyme is abundant and widely distributed. Its sequence is highly conserved. It is the first identified and only known mammalian member of the M18 family of metalloproteinases. We are studying the relationship of its subunit structure to its catalytic activity, the nature of its endogenous substrates and the regulation of its enzymatic activity.