4P3D

MT1-MMP:Fab complex (Form II)

4P3D の概要

• エントリーDOI: 10.2210/pdb4p3d/pdb
• 関連するPDBエントリー: 4P3C
• 分子名称: Heavy Chain Fab fragment of antibody LEM-2/15, Light Chain Fab fragment of antibody LEM-2/15, Matrix metalloproteinase-14, ... (9 entities in total)
• 機能のキーワード: immune system
• 由来する生物種: Mus musculus; 詳細
• 細胞内の位置: Membrane ; Single-pass type I membrane protein : P50281
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 98987.47

構造登録者

Rozenberg, H.,Udi, Y.,Sagi, I. (登録日: 2014-03-07, 公開日: 2014-12-17, 最終更新日: 2024-10-30)

主引用文献

Udi, Y.,Grossman, M.,Solomonov, I.,Dym, O.,Rozenberg, H.,Moreno, V.,Cuniasse, P.,Dive, V.,Arroyo, A.G.,Sagi, I.
Inhibition mechanism of membrane metalloprotease by an exosite-swiveling conformational antibody.
Structure, 23:104-115, 2015

PubMed 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.

PubMed: 25482542
DOI: 10.1016/j.str.2014.10.012

実験手法

X-RAY DIFFRACTION (1.949 Å)