1bht

NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTORNK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR

Structural highlights 1bht 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. Method: X-ray diffraction, Resolution 2Å Ligands: , 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. 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 BACKGROUND: Hepatocyte growth factor (HGF) is a mitogen for hepatocytes and has also been implicated as an epithelial morphogen in tumor invasion. HGF activates its specific cellular receptor, c-met, through an aggregation mechanism potentiated by heparan sulfate glycosaminoglycans. HGF consists of an N-terminal (N) domain, four kringle domains (the first of which carries receptor-binding determinants), and an inactive serine-protease-like domain. NK1, a naturally occurring fragment of HGF, acts as an antagonist of HGF in the absence of heparin. RESULTS: The N domain of NK1 consists of a central five-stranded antiparallel beta sheet flanked by an alpha helix and a two-stranded beta ribbon. The overall N domain structure in the context of the NK1 fragment is similar to the structure of the isolated domain; two lysines and an arginine residue coordinate a bound sulfate ion. The NK1 kringle domain is homologous to kringle 4 from plasminogen, except that the lysine-binding pocket is altered by the insertion of a glycine residue. Here, a HEPES molecule is bound in the pocket. The asymmetric unit of the crystal contains a 'head-to-tail' NK1 dimer. We use this dimer to propose a model of the NK2 fragment of HGF. CONCLUSIONS: A cluster of exposed lysine and arginine residues in or near the hairpin-loop region of the N domain might form part of the NK1 heparin-binding site. In our NK2 model, both kringle domains pack loosely against the N domain, and a long, positively charged groove lines the interface. This groove might be involved in glycosaminoglycan binding. The HGF receptor-binding determinants are clustered near the binding pocket of the first kringle domain, opposite the N domain. Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.,Ultsch M, Lokker NA, Godowski PJ, de Vos AM Structure. 1998 Nov 15;6(11):1383-93. PMID:9817840 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hepatocyte growth factor

spinqualitylabelsall models 1bht, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image