2MQS
Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and Development: Spin Labels to Structure
Summary for 2MQS
| Entry DOI | 10.2210/pdb2mqs/pdb |
| NMR Information | BMRB: 25048 |
| Descriptor | Matrix metalloproteinase-14, THP_L_and_M_chain, THP_T_chain (3 entities in total) |
| Functional Keywords | protein/protein, hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 32744.80 |
| Authors | Zhao, Y.,Marcink, T.,Van Doren, S.R. (deposition date: 2014-06-26, release date: 2015-02-11, Last modification date: 2023-06-14) |
| Primary citation | Zhao, Y.,Marcink, T.C.,Sanganna Gari, R.R.,Marsh, B.P.,King, G.M.,Stawikowska, R.,Fields, G.B.,Van Doren, S.R. Transient collagen triple helix binding to a key metalloproteinase in invasion and development. Structure, 23:257-269, 2015 Cited by PubMed Abstract: Skeletal development and invasion by tumor cells depends on proteolysis of collagen by the pericellular metalloproteinase MT1-MMP. Its hemopexin-like (HPX) domain binds to collagen substrates to facilitate their digestion. Spin labeling and paramagnetic nuclear magnetic resonance (NMR) detection have revealed how the HPX domain docks to collagen I-derived triple helix. Mutations impairing triple-helical peptidase activity corroborate the interface. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Part of the interface emerges as unique and potentially targetable for selective inhibition. The triple helix crosses the junction of blades I and II at a 45° angle to the symmetry axis of the HPX domain, placing the scissile Gly∼Ile bond near the HPX domain and shifted ∼25 Å from MMP-1 complexes. This raises the question of the MT1-MMP catalytic domain folding over the triple helix during catalysis, a possibility accommodated by the flexibility between domains suggested by atomic force microscopy images. PubMed: 25651059DOI: 10.1016/j.str.2014.11.021 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
