Active Site Specificity Profiling of the Matrix Metalloproteinase Family: Proteomic Identification of 4,300 Cleavage Sites by MMPs 1, 2, 3, 7, 8, 9, 12, 13, and 14.

Background: The active site of matrix metalloproteinases (MMPs) is highly conserved, complicating the rational design of specific substrates and inhibitors for individual family members. Results: Active site specificity profiles of 9 MMPs were determined using high throughput Proteomic Identification of protease Cleavage Sites (PICS). Conclusion: Subtle specificity divergences distinguish individual MMP family members. Significance: Understanding individual MMP cleavage site specificities will bolster the design of MMP specific activity assays and targeted inhibitory drugs.