4o3u

Zymogen HGF-beta/MET with Zymogen Activator Peptide ZAP2.3

spinqualitylabelsall models 4o3u, resolution 3.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4o3u is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.04Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HGF_HUMAN Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:608265. A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Function HGF_HUMAN Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. Publication Abstract from PubMed Stimulation of hepatocyte growth factor (HGF) signaling through the Met receptor is an attractive approach for promoting tissue repair and preventing fibrosis. Using structure-guided peptide phage display combined with an activity-based sorting strategy, we engineered allosteric activators of zymogen-like pro-HGF to bypass proteolytic activation and reversibly stimulate pro-HGF signaling through Met. Biochemical, structural and biological data showed that zymogen activator peptides (ZAPtides) potently and selectively bind the activation pocket within the serine protease-like beta-chain of pro-HGF and display titratable activation of pro-HGF-dependent Met signaling, leading to cell survival and migration. To further demonstrate the versatility of our ZAPtide platform, we identified allosteric activators for pro-macrophage stimulating protein and a zymogen serine protease, Protein C, which also provides evidence for target selectivity. These studies reveal that ZAPtides use molecular mimicry of the trypsin-like N-terminal insertion mechanism and establish a new paradigm for selective pharmacological activation of plasminogen-related growth factors and zymogen serine proteases. An allosteric switch for pro-HGF/Met signaling using zymogen activator peptides.,Landgraf KE, Steffek M, Quan C, Tom J, Yu C, Santell L, Maun HR, Eigenbrot C, Lazarus RA Nat Chem Biol. 2014 May 25. doi: 10.1038/nchembio.1533. PMID:24859116 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hepatocyte growth factor Hepatocyte growth factor receptor 3D structures

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