1vr2: Difference between revisions
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'''HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2 (KDR) KINASE DOMAIN''' | '''HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2 (KDR) KINASE DOMAIN''' | ||
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[[Category: Villafranca, J.]] | [[Category: Villafranca, J.]] | ||
[[Category: Wickersham, J.]] | [[Category: Wickersham, J.]] | ||
[[Category: | [[Category: Tyrosine kinase]] | ||
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Revision as of 12:49, 3 May 2008
HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2 (KDR) KINASE DOMAIN
OverviewOverview
BACKGROUND: Angiogenesis is involved in tumor growth, macular degeneration, retinopathy and other diseases. Vascular endothelial growth factor (VEGF) stimulates angiogenesis by binding to specific receptors (VEGFRs) on the surface of vascular endothelial cells. VEGFRs are receptor tyrosine kinases that, like the platelet-derived growth factor receptors (PDGFRs), contain a large insert within the kinase domain. RESULTS: We report here the generation, kinetic characterization, and 2.4 A crystal structure of the catalytic kinase domain of VEGF receptor 2 (VEGFR2). This protein construct, which lacks 50 central residues of the 68-residue kinase insert domain (KID), has comparable kinase activity to constructs containing the entire KID. The crystal structure, determined in an unliganded phosphorylated state, reveals an overall fold and catalytic residue positions similar to those observed in other tyrosine-kinase structures. The kinase activation loop, autophosphorylated on Y1059 prior to crystallization, is mostly disordered; however, a portion of it occupies a position inhibitory to substrate binding. The ends of the KID form a beta-like structure, not observed in other known tyrosine kinase structures, that packs near to the kinase C terminus. CONCLUSIONS: The majority of the VEGFR2 KID residues are not necessary for kinase activity. The unique structure observed for the ends of the KID may also occur in other PDGFR family members and may serve to properly orient the KID for signal transduction. This VEGFR2 kinase structure provides a target for design of selective anti-angiogenic therapeutic agents.
About this StructureAbout this Structure
1VR2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis., McTigue MA, Wickersham JA, Pinko C, Showalter RE, Parast CV, Tempczyk-Russell A, Gehring MR, Mroczkowski B, Kan CC, Villafranca JE, Appelt K, Structure. 1999 Mar 15;7(3):319-30. PMID:10368301 Page seeded by OCA on Sat May 3 12:49:03 2008