2mqs

Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and Development: Spin Labels to Structure

spinqualitylabelsall models 2mqs, 15 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mqs is a 4 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: HYP Gene: MMP14 (HUMAN) Activity: Membrane-type matrix metalloproteinase-1, with EC number 3.4.24.80 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MMP14_HUMAN] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Matrix metalloproteinase

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