4p3c

Publication Abstract from PubMed

Membrane type 1 metalloprotease (MT1-MMP) is a membrane-anchored, zinc-dependent protease. MT1-MMP is an important mediator of cell migration and invasion, and overexpression of this enzyme has been correlated with the malignancy of various tumor types. Therefore, modulators of MT1-MMP activity are proposed to possess therapeutic potential in numerous invasive diseases. Here we report the inhibition mode of MT1-MMP by LEM-2/15 antibody, which targets a surface epitope of MT1-MMP. Specifically, the crystal structures of Fab LEM-2/15 in complex with the MT1-MMP surface antigen suggest that conformational swiveling of the enzyme surface loop is required for effective binding and consequent inhibition of MT1-MMP activity on the cell membrane. This inhibition mechanism appears to be effective in controlling active MT1-MMP in endothelial cells and at the leading edge of migratory cancer cells.

Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational Antibody.,Udi Y, Grossman M, Solomonov I, Dym O, Rozenberg H, Moreno V, Cuniasse P, Dive V, Arroyo AG, Sagi I Structure. 2014 Dec 3. pii: S0969-2126(14)00357-8. doi:, 10.1016/j.str.2014.10.012. PMID:25482542^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.