2N8R

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

Summary for 2N8R

• Entry DOI: 10.2210/pdb2n8r/pdb
• Related: 2poj
• NMR Information: BMRB: 25859
• Descriptor: Macrophage metalloelastase, Collagen triple helix repeat family protein, ZINC ION, ... (5 entities in total)
• Functional Keywords: collagenolysis, matrix petalloproteinase, hydrolase-structural protein complex, hydrolase/structural protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix : P39900
• Total number of polymer chains: 4
• Total formula weight: 28360.81

Authors

Prior, S.H.,Van Doren, S.R. (deposition date: 2015-10-24, release date: 2016-02-24, Last modification date: 2025-03-26)

Primary citation

Prior, S.H.,Byrne, T.S.,Tokmina-Roszyk, D.,Fields, G.B.,Van Doren, S.R.
Path to Collagenolysis: COLLAGEN V TRIPLE-HELIX MODEL BOUND PRODUCTIVELY AND IN ENCOUNTERS BY MATRIX METALLOPROTEINASE-12.
J.Biol.Chem., 291:7888-7901, 2016

PubMed 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 ∼1,080 Å(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∼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.

PubMed: 26887942
DOI: 10.1074/jbc.M115.703124

Experimental method

SOLUTION NMR