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| {{STRUCTURE_1p14| PDB=1p14 | SCENE= }} | | {{STRUCTURE_1p14| PDB=1p14 | SCENE= }} |
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| '''Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase'''
| | ===Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase=== |
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| ==Overview==
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| Tyrosine 984 in the juxtamembrane region of the insulin receptor, between the transmembrane helix and the cytoplasmic tyrosine kinase domain, is conserved among all insulin receptor-like proteins from hydra to humans. Crystallographic studies of the tyrosine kinase domain and proximal juxtamembrane region reveal that Tyr-984 interacts with several other conserved residues in the N-terminal lobe of the kinase domain, stabilizing a catalytically nonproductive position of alpha-helix C. Steady-state kinetics measurements on the soluble kinase domain demonstrate that replacement of Tyr-984 with phenylalanine results in a 4-fold increase in kcat in the unphosphorylated (basal state) enzyme. Moreover, mutation of Tyr-984 in the full-length insulin receptor results in significantly elevated receptor phosphorylation levels in cells, both in the absence of insulin and following insulin stimulation. These data demonstrate that Tyr-984 plays an important structural role in maintaining the quiescent, basal state of the insulin receptor. In addition, the structural studies suggest a possible target site for small molecule activators of the insulin receptor, with potential use in the treatment of noninsulin-dependent diabetes mellitus.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12707268}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12707268 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12707268}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Receptor]] | | [[Category: Receptor]] |
| [[Category: Tyrosine kinase]] | | [[Category: Tyrosine kinase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:32:58 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:48:01 2008'' |
