Pyrone-based inhibitors of metalloproteinase types 2 and 3 may work as conformation-selective inhibitors.

ABSTRACT: Matrix metalloproteinases are zinc-containing enzymes capable of degrading all components of the extracellular matrix. Owing to their role in human disease, matrix metalloproteinase have been the subject of extensive study. A bioinorganic approach was recently used to identify novel inhibitors based on a maltol zinc-binding group, but accompanying molecular-docking studies failed to explain why one of these inhibitors, AM-6, had approximately 2500-fold selectivity for MMP-3 over MMP-2. A number of studies have suggested that the matrix-metalloproteinase active site is highly flexible, leading some to speculate that differences in active-site flexibility may explain inhibitor selectivity. To extend the bioinorganic approach in a way that accounts for MMP-2 and MMP-3 dynamics, we here invest

SUBMITTER: Durrant JD 

PROVIDER: S-EPMC3135671 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature