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PDBsum entry 4p3c
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Immune system
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PDB id
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4p3c
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Contents |
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218 a.a.
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218 a.a.
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13 a.a.
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References listed in PDB file
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Key reference
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Title
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Inhibition mechanism of membrane metalloprotease by an exosite-Swiveling conformational antibody.
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Authors
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Y.Udi,
M.Grossman,
I.Solomonov,
O.Dym,
H.Rozenberg,
V.Moreno,
P.Cuniasse,
V.Dive,
A.G.Arroyo,
I.Sagi.
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Ref.
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Structure, 2015,
23,
104-115.
[DOI no: ]
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PubMed id
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Abstract
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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.
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