Structure of human pro-matrix metalloproteinase-2: Activation mechanism revealed

Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases ch aracterized by abnormal connective tissue turnover. MMPs are expressed as L atent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure o f proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of Loops essential for pro peptide stability.