2N8R: Productive complex between MMP-12 and synthetic triple-helical collagen, revealed through paramagnetic NMR

Citation:
Abstract
Collagenolysis is essential in extracellular matrix homeostasis, but its structural basis has long been shrouded in mystery. We have developed a novel docking strategy guided by paramagnetic NMR that positions a triple-helical collagen V mimic (synthesized with nitroxide spin labels) in the active site of the catalytic domain of matrix metalloproteinase-12 (MMP-12 or macrophage metalloelastase) primed for catalysis. The collagenolytically productive complex forms by utilizing seven distinct subsites that traverse the entire length of the active site. These subsites bury approximately 1,080 A(2)of surface area, over half of which is contributed by the trailing strand of the synthetic collagen V mimic, which also appears to ligate the catalytic zinc through the glycine carbonyl oxygen of its scissile G approximately VV triplet. Notably, the middle strand also occupies the full length of the active site where it contributes extensive interfacial contacts with five subsites. This work identifies, for the first time, the productive and specific interactions of a collagen triple helix with an MMP catalytic site. The results uniquely demonstrate that the active site of the MMPs is wide enough to accommodate two strands from collagen triple helices. Paramagnetic relaxation enhancements also reveal an extensive array of encounter complexes that form over a large part of the catalytic domain. These transient complexes could possibly facilitate the formation of collagenolytically active complexes via directional Brownian tumbling.
PDB ID: 2N8RDownload
MMDB ID: 136647
PDB Deposition Date: 2015/10/24
Updated in MMDB: 2016/06
Experimental Method:
solution nmr
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 2N8R: tetrameric; determined by author
Molecular Components in 2N8R
Label Count Molecule
Proteins (4 molecules)
1
Macrophage Metalloelastase(Gene symbol: MMP12)
Molecule annotation
3
Collagen Triple Helix Repeat Family Protein
Molecule annotation
Chemicals (5 molecules)
1
2
2
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.