Mapping the Binding Site for Matrix Metalloproteinase on the N-Terminal Domain of the Tissue Inhibitor of Metalloproteinases-2 by NMR Chemical Shift Perturbation

Publisher Website
Google Scholar
Abstract
Changes in the NMR chemical shift of backbone amide nuclei (1H and 15N) have been used to map the matrix metalloproteinase (MMP) binding site on the N-terminal domain of the tissue inhibitor of metalloproteinase-2 (N-TIMP-2). Amide chemical shift changes were measured on formation of a stable complex with the catalytic domain of stromelysin-1 (N-MMP-3). Residues with significantly shifted amide signals mapped specifically to a broad site covering one face of the molecule. This site (the MMP binding site) consists primarily of residues 1−11, 27−41, 68−73, 87−90, and 97−104. The site overlaps with the OB-fold binding site seen in other proteins that share the same five-stranded β-barrel topology. Sequence conservation data and recent site-directed mutagenesis studies are discussed in relation to the MMP binding site identified in this work.