5UE2

proMMP-7 with heparin octasaccharide bridging between domains

5UE2 の概要

• エントリーDOI: 10.2210/pdb5ue2/pdb
• 関連するPDBエントリー: 2MZE
• NMR情報: BMRB: 25485
• 分子名称: Matrilysin, 2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: glycan complex with protein, enzyme complex with heparin oligosaccharide, zymogen, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30128.01

構造登録者

Fulcher, Y.G.,Prior, S.H.,Linhardt, R.J.,Van Doren, S.R. (登録日: 2016-12-29, 公開日: 2017-07-19, 最終更新日: 2024-05-22)

主引用文献

Fulcher, Y.G.,Prior, S.H.,Masuko, S.,Li, L.,Pu, D.,Zhang, F.,Linhardt, R.J.,Van Doren, S.R.
Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7.
Structure, 25:1100-1110.e5, 2017

PubMed Abstract: Heparan sulfate proteoglycans activate the matrix metalloproteinase-7 zymogen (proMMP-7) and recruit it in order to shed proteins from cell surfaces. This occurs in uterine and mammary epithelia, bacterial killing, lung healing, and tumor cell signaling. Basic tracks on proMMP-7 recognize polyanionic heparin, according to nuclear magnetic resonance and mutations disruptive of maturation. Contacts and proximity measurements guided docking of a heparin octasaccharide to proMMP-7. The reducing end fits into a basic pocket in the pro-domain while the chain continues toward the catalytic domain. Another oligosaccharide traverses a basic swath remote on the catalytic domain and inserts its reducing end into a slot formed with the basic C terminus. This latter association appears to support allosteric acceleration of proteolysis. The modes of binding account for extended, heterogeneous assemblies of proMMP-7 with heparinoids during maturation and for bridging to pro-α-defensins and proteoglycans. These associations support proteolytic release of activities at epithelial cell surfaces.

PubMed: 28648610
DOI: 10.1016/j.str.2017.05.019

実験手法

SOLUTION NMR