| Literature DB >> 25482542 |
Yael Udi1, Moran Grossman1, Inna Solomonov1, Orly Dym2, Haim Rozenberg2, Vanessa Moreno3, Philippe Cuniasse4, Vincent Dive4, Alicia García Arroyo3, Irit Sagi5.
Abstract
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.Entities:
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Year: 2014 PMID： 25482542 DOI： 10.1016/j.str.2014.10.012
Source DB: PubMed Journal: Structure ISSN： 0969-2126 Impact factor: 5.006