2mqs

Publication Abstract from PubMed

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 degrees angle to the symmetry axis of the HPX domain, placing the scissile Gly approximately Ile bond near the HPX domain and shifted approximately 25 A 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.

Transient collagen triple helix binding to a key metalloproteinase in invasion and development.,Zhao Y, Marcink TC, Sanganna Gari RR, Marsh BP, King GM, Stawikowska R, Fields GB, Van Doren SR Structure. 2015 Feb 3;23(2):257-69. doi: 10.1016/j.str.2014.11.021. PMID:25651059^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.