5UE5

proMMP-7 with heparin octasaccharide bound to the catalytic domain

Summary for 5UE5

• Entry DOI: 10.2210/pdb5ue5/pdb
• Related: 2MZE 5UE2
• NMR Information: BMRB: 25485
• Descriptor: 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)
• Functional Keywords: glycan complex with protein, enzyme complex with heparin oligosaccharide, zymogen, allosteric effector site, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 30128.01

Authors

Fulcher, Y.G.,Prior, S.H.,Linhardt, R.J.,Van Doren, S.R. (deposition date: 2016-12-29, release date: 2017-07-19, Last modification date: 2024-05-01)

Primary citation

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

Experimental method

SOLUTION NMR