1r1w
From Proteopedia
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| - | [[Image:1r1w.jpg|left|200px]] | + | [[Image:1r1w.jpg|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE GROWTH FACTOR RECEPTOR C-MET''' | + | {{Structure |
| + | |PDB= 1r1w |SIZE=350|CAPTION= <scene name='initialview01'>1r1w</scene>, resolution 1.80Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | ||
| + | |GENE= MET ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE GROWTH FACTOR RECEPTOR C-MET''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R1W is a [ | + | 1R1W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R1W OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a., Schiering N, Knapp S, Marconi M, Flocco MM, Cui J, Perego R, Rusconi L, Cristiani C, Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12654-9. Epub 2003 Oct 14. PMID:[http:// | + | Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a., Schiering N, Knapp S, Marconi M, Flocco MM, Cui J, Perego R, Rusconi L, Cristiani C, Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12654-9. Epub 2003 Oct 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14559966 14559966] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:45:46 2008'' |
Revision as of 11:45, 20 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | MET (Homo sapiens) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE GROWTH FACTOR RECEPTOR C-MET
Contents |
Overview
The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique C-terminal tail of c-Met (supersite). There is a strong link between aberrant c-Met activity and oncogenesis, which makes this kinase an important cancer drug target. The furanosylated indolocarbazole K-252a belongs to a family of microbial alkaloids that also includes staurosporine. It was recently shown to be a potent inhibitor of c-Met. Here we report the crystal structures of an unphosphorylated c-Met kinase domain harboring a human cancer mutation and its complex with K-252a at 1.8-A resolution. The structure follows the well established architecture of protein kinases. It adopts a unique, inhibitory conformation of the activation loop, a catalytically noncompetent orientation of helix alphaC, and reveals the complete C-terminal docking site. The first SH2-binding motif (1349YVHV) adopts an extended conformation, whereas the second motif (1356YVNV), a binding site for Grb2-SH2, folds as a type II Beta-turn. The intermediate portion of the supersite (1353NATY) assumes a type I Beta-turn conformation as in an Shc-phosphotyrosine binding domain peptide complex. K-252a is bound in the adenosine pocket with an analogous binding mode to those observed in previously reported structures of protein kinases in complex with staurosporine.
Disease
Known diseases associated with this structure: Autism, suseptibility to, 9 OMIM:[164860], Hepatocellular carcinoma, childhood type OMIM:[164860], Renal cell carcinoma, papillary, familial and sporadic OMIM:[164860]
About this Structure
1R1W is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a., Schiering N, Knapp S, Marconi M, Flocco MM, Cui J, Perego R, Rusconi L, Cristiani C, Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12654-9. Epub 2003 Oct 14. PMID:14559966
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