1p14

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[[Image:1p14.gif|left|200px]]
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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'''
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===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.
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The line below this paragraph, {{ABSTRACT_PUBMED_12707268}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12707268 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12707268}}
==About this Structure==
==About this Structure==
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[[Category: Receptor]]
[[Category: Receptor]]
[[Category: Tyrosine kinase]]
[[Category: Tyrosine kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:32:58 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:48:01 2008''

Revision as of 09:48, 29 July 2008

Image:1p14.png

Template:STRUCTURE 1p14

Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase

Template:ABSTRACT PUBMED 12707268

About this Structure

1P14 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural and biochemical evidence for an autoinhibitory role for tyrosine 984 in the juxtamembrane region of the insulin receptor., Li S, Covino ND, Stein EG, Till JH, Hubbard SR, J Biol Chem. 2003 Jul 11;278(28):26007-14. Epub 2003 Apr 21. PMID:12707268

Page seeded by OCA on Tue Jul 29 12:48:01 2008

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