Human proteases regulate numerous biological processes. Most are stored as inactive proenzymes that are activated either by upstream processes or by self-proteolysis. Wolan et al. have identified a small molecule that activates the apoptotic procaspases-3 and -6. These caspases are homodimers, and the compound probably competitively inhibits one active site but stabilizes an on-state conformation that promotes self-cleavage by the unoccupied site. It may thus be possible to find other small-molecule activators for other proenzymes that should facilitate functional and mechanistic studies.
D. W. Wolan, J. A. Zorn, D. C. Gray, J. A. Wells, Small-molecule activators of a proenzyme. Science 326, 853–858 (2009). [Abstract] [Full Text]
