2qj2 | pdb_00002qj2

A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist

spinqualitylabelsall models 2qj2, resolution 1.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2qj2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 1nk1, 1gp9, 1gmn, 1gmo, 1bht, 2hgf, 2qj4 Gene: HGF, HPTA (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Hepatocyte growth factor (HGF) activates the Met receptor tyrosine kinase by binding and promoting receptor dimerization. Here we describe a mechanistic basis for designing Met antagonists based on NK1, a natural variant of HGF containing the N-terminal and the first kringle domain. Through detailed biochemical and structural analyses, we demonstrate that both mouse and human NK1 induce Met dimerization via a conserved NK1 dimer interface. Mutations designed to alter the NK1 dimer interface abolish its ability to promote Met dimerization but retain full Met-binding activity. Importantly, these NK1 mutants act as Met antagonists by inhibiting HGF-mediated cell scattering, proliferation, branching, and invasion. The ability to separate the Met-binding activity of NK1 from its Met dimerization activity thus provides a rational basis for designing Met antagonists. This strategy of antagonist design may be applicable for other growth factor receptors by selectively abolishing the receptor activation ability but not the receptor binding of the growth factors. A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist.,Tolbert WD, Daugherty J, Gao C, Xie Q, Miranti C, Gherardi E, Woude GV, Xu HE Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14592-7. Epub 2007 Sep 5. PMID:17804794 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hepatocyte growth factor

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