2pvf: Difference between revisions
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==Overview== | ==Overview== | ||
Activating mutations in the tyrosine kinase domain of receptor tyrosine | Activating mutations in the tyrosine kinase domain of receptor tyrosine kinases (RTKs) cause cancer and skeletal disorders. Comparison of the crystal structures of unphosphorylated and phosphorylated wild-type FGFR2 kinase domains with those of seven unphosphorylated pathogenic mutants reveals an autoinhibitory "molecular brake" mediated by a triad of residues in the kinase hinge region of all FGFRs. Structural analysis shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic mutations activate FGFRs and other RTKs by disengaging the brake either directly or indirectly. | ||
==Disease== | |||
Known diseases associated with this structure: Antley-Bixler syndrome, 207410 ( OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Apert syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Beare-Stevenson cutis gyrata syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Craniofacial-skeletal-dermatologic dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Craniosynostosis, nonspecific OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Crouzon syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Gastric cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Jackson-Weiss syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Pfeiffer syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Saethre-Chotzen syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:33:29 2008'' | ||
Revision as of 19:33, 21 February 2008
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Crystal Structure of Tyrosine Phosphorylated Activated FGF Receptor 2 (FGFR2) Kinase Domain in Complex with ATP Analog and Substrate Peptide
OverviewOverview
Activating mutations in the tyrosine kinase domain of receptor tyrosine kinases (RTKs) cause cancer and skeletal disorders. Comparison of the crystal structures of unphosphorylated and phosphorylated wild-type FGFR2 kinase domains with those of seven unphosphorylated pathogenic mutants reveals an autoinhibitory "molecular brake" mediated by a triad of residues in the kinase hinge region of all FGFRs. Structural analysis shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic mutations activate FGFRs and other RTKs by disengaging the brake either directly or indirectly.
DiseaseDisease
Known diseases associated with this structure: Antley-Bixler syndrome, 207410 ( OMIM:[176943], Apert syndrome OMIM:[176943], Beare-Stevenson cutis gyrata syndrome OMIM:[176943], Craniofacial-skeletal-dermatologic dysplasia OMIM:[176943], Craniosynostosis, nonspecific OMIM:[176943], Crouzon syndrome OMIM:[176943], Gastric cancer, somatic OMIM:[176943], Jackson-Weiss syndrome OMIM:[176943], Pfeiffer syndrome OMIM:[176943], Saethre-Chotzen syndrome OMIM:[176943]
About this StructureAbout this Structure
2PVF is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
ReferenceReference
A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases., Chen H, Ma J, Li W, Eliseenkova AV, Xu C, Neubert TA, Miller WT, Mohammadi M, Mol Cell. 2007 Sep 7;27(5):717-30. PMID:17803937
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