1p14: Difference between revisions
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New page: left|200px<br /> <applet load="1p14" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p14, resolution 1.90Å" /> '''Crystal structure o... |
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[[Image:1p14.gif|left|200px]]<br /> | [[Image:1p14.gif|left|200px]]<br /><applet load="1p14" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1p14" size=" | |||
caption="1p14, resolution 1.90Å" /> | caption="1p14, resolution 1.90Å" /> | ||
'''Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase'''<br /> | '''Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase'''<br /> | ||
==Overview== | ==Overview== | ||
Tyrosine 984 in the juxtamembrane region of the insulin receptor, between | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1P14 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http:// | 1P14 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P14 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Covino, N | [[Category: Covino, N D.]] | ||
[[Category: Hubbard, S | [[Category: Hubbard, S R.]] | ||
[[Category: Li, S.]] | [[Category: Li, S.]] | ||
[[Category: Stein, E | [[Category: Stein, E G.]] | ||
[[Category: Till, J | [[Category: Till, J H.]] | ||
[[Category: catalysis]] | [[Category: catalysis]] | ||
[[Category: mutant]] | [[Category: mutant]] | ||
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[[Category: tyrosine kinase]] | [[Category: tyrosine kinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:23:54 2008'' | ||
