2MZE

NMR Solution Structure of the PRO Form of Human Matrilysin (proMMP-7)

2MZE の概要

• エントリーDOI: 10.2210/pdb2mze/pdb
• 関連するPDBエントリー: 1mmp 1mmq 1mmr 2y6c 2y6d
• 分子名称: Matrilysin, CALCIUM ION, ZINC ION (3 entities in total)
• 機能のキーワード: zymogen, hydrolase, metalloenzyme
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : P09237
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28123.55

構造登録者

Prior, S.H.,Fulcher, Y.G.,Van Doren, S.R. (登録日: 2015-02-11, 公開日: 2015-11-11, 最終更新日: 2024-05-15)

主引用文献

Prior, S.H.,Fulcher, Y.G.,Koppisetti, R.K.,Jurkevich, A.,Van Doren, S.R.
Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors.
Structure, 23:2099-2110, 2015

PubMed Abstract: Matrix metalloproteinase-7 (MMP-7) sheds signaling proteins from cell surfaces to activate bacterial killing, wound healing, and tumorigenesis. The mechanism targeting soluble MMP-7 to membranes has been investigated. Nuclear magnetic resonance structures of the zymogen, free and bound to membrane mimics without and with anionic lipid, reveal peripheral binding to bilayers through paramagnetic relaxation enhancements. Addition of cholesterol sulfate partially embeds the protease in the bilayer, restricts its diffusion, and tips the active site away from the bilayer. Its insertion of hydrophobic residues organizes the lipids, pushing the head groups and sterol sulfate outward toward the enzyme's positive charge on the periphery of the enlarged interface. Fluorescence probing demonstrates a similar mode of binding to plasma membranes and internalized vesicles of colon cancer cells. Binding of bilayered micelles induces allosteric activation and conformational change in the auto-inhibitory peptide and the adjacent scissile site, illustrating a potential intermediate in the activation of the zymogen.

PubMed: 26439767
DOI: 10.1016/j.str.2015.08.013

実験手法

SOLUTION NMR