Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7.
Structure
; 25(7): 1100-1110.e5, 2017 07 05.
Article
in En
| MEDLINE
| ID: mdl-28648610
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Metalloendopeptidases
/
Heparin
/
Enzyme Precursors
/
Molecular Docking Simulation
Limits:
Humans
Language:
En
Journal:
Structure
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Estados Unidos