AN ANALYSIS OF THE CONFORMATIONAL-CHANGES THAT ACCOMPANY THE ACTIVATION AND INHIBITION OF GELATINASE-A

The latent precursors of the matrix metalloproteinases (MMPs) are conv erted by (4-aminophenylmercuric)acetate to active forms that lose thei r propeptide as a result of autolysis, C.D. and an active site mutant of progelatinase A (MMP2) were used to demonstrate that, although prop eptide removal is accompanied by a decrease in the enzyme's beta-sheet content, the initial activation is achieved with only minor modificat ions to the conformation, Mixing activated gelatinase A with the natur al inhibitor, TIMP-1, resulted in conformational changes that were abs ent when a synthetic inhibitor was used, The relevance of these result s to MR IP activation and inhibition is discussed.