4p3d

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MT1-MMP:Fab complex (Form II)

Structural highlights

4p3d is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.949Å
Ligands:CL, EDO, EPE, GOL, MG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A2NHM3_MOUSE

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.

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Citations
12 reviews cite this structure
The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma.
Fields et al. (2019)
11 more
18 other articles
No citations found

See Also

References

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

Contents


PDB ID 4p3d

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OCA

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