1jqh: Difference between revisions
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'''IGF-1 receptor kinase domain''' | {{Structure | ||
|PDB= 1jqh |SIZE=350|CAPTION= <scene name='initialview01'>1jqh</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER'>ANP</scene> | |||
|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= | |||
}} | |||
'''IGF-1 receptor kinase domain''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1JQH is a [ | 1JQH 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=1JQH OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation., Pautsch A, Zoephel A, Ahorn H, Spevak W, Hauptmann R, Nar H, Structure. 2001 Oct;9(10):955-65. PMID:[http:// | Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation., Pautsch A, Zoephel A, Ahorn H, Spevak W, Hauptmann R, Nar H, Structure. 2001 Oct;9(10):955-65. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11591350 11591350] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: protein kinase fold]] | [[Category: protein kinase fold]] | ||
''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 12:07:01 2008'' | ||
Revision as of 13:07, 20 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| 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 | ||||||
IGF-1 receptor kinase domain
OverviewOverview
BACKGROUND: The insulin-like growth-factor-1 (IGF-1) receptor, which is widely expressed in cells that have undergone oncogenic transformation, is emerging as a novel target in cancer therapy. IGF-1-induced receptor activation results in autophosphorylation of cytoplasmic kinase domains and enhances their capability to phosphorylate downstream substrates. Structures of the homologous insulin receptor kinase (IRK) exist in an open, unphosphorylated form and a closed, trisphosphorylated form. RESULTS: We have determined the 2.1 A crystal structure of the IGF-1 receptor protein tyrosine kinase domain phosphorylated at two tyrosine residues within the activation loop (IGF-1RK2P) and bound to an ATP analog. The ligand is not in a conformation compatible with phosphoryl transfer, and the activation loop is partially disordered. Compared to the homologous insulin receptor kinase, IGF-1RK2P is trapped in a half-closed, previously unobserved conformation. Observed domain movements can be dissected into two orthogonal rotational components. CONCLUSIONS: Conformational changes upon kinase activation are triggered by the degree of phosphorylation and are crucially dependent on the conformation of the proximal end of the kinase activation loop. This IGF-1RK structure will provide a molecular basis for the design of selective antioncogenic therapeutic agents.
DiseaseDisease
Known disease associated with this structure: Intrauterine and postnatal growth retardation OMIM:[147370]
About this StructureAbout this Structure
1JQH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation., Pautsch A, Zoephel A, Ahorn H, Spevak W, Hauptmann R, Nar H, Structure. 2001 Oct;9(10):955-65. PMID:11591350
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