Identification of collagen binding domain residues that govern catalytic activities of matrix metalloproteinase-2 (MMP-2).

ABSTRACT: An innovative approach to enhance the selectivity of matrix metalloproteinase (MMP) inhibitors comprises targeting these inhibitors to catalytically required substrate binding sites (exosites) that are located outside the catalytic cleft. In MMP-2, positioning of collagen substrate molecules occurs via a unique fibronectin-like domain (CBD) that contains three distinct modular collagen binding sites. To characterize the contributions of these exosites to gelatinolysis by MMP-2, seven MMP-2 variants were generated with single, or concurrent double and triple alanine substitutions in the three fibronectin type II modules of the CBD. Circular dichroism spectroscopy verified that recombinant MMP-2 wild-type (WT) and variants had the same fold. Moreover, the MMP-2 WT and variants had the same a

SUBMITTER: Mikhailova M 

PROVIDER: S-EPMC3513585 | biostudies-literature | 2012 Sep-Oct

REPOSITORIES: biostudies-literature