3bu3

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[[Image:3bu3.jpg|left|200px]]
[[Image:3bu3.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 3bu3 |SIZE=350|CAPTION= <scene name='initialview01'>3bu3</scene>, resolution 1.65&Aring;
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The line below this paragraph, containing "STRUCTURE_3bu3", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= INSR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_3bu3| PDB=3bu3 | SCENE= }}
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|RELATEDENTRY=[[3bu5|3BU5]], [[3bu6|3BU6]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bu3 OCA], [http://www.ebi.ac.uk/pdbsum/3bu3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bu3 RCSB]</span>
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}}
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'''Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide'''
'''Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide'''
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[[Category: Hubbard, S R.]]
[[Category: Hubbard, S R.]]
[[Category: Wu, J.]]
[[Category: Wu, J.]]
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[[Category: alternative splicing]]
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[[Category: Alternative splicing]]
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[[Category: atp-binding]]
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[[Category: Atp-binding]]
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[[Category: carbohydrate metabolism]]
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[[Category: Carbohydrate metabolism]]
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[[Category: cleavage on pair of basic residue]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: diabetes mellitus]]
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[[Category: Diabetes mellitus]]
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[[Category: disease mutation]]
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[[Category: Disease mutation]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: insulin receptor]]
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[[Category: Insulin receptor]]
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[[Category: irk]]
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[[Category: Irk]]
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[[Category: irs2]]
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[[Category: Irs2]]
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[[Category: kinase]]
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[[Category: Kinase]]
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[[Category: krlb]]
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[[Category: Krlb]]
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[[Category: membrane]]
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[[Category: Membrane]]
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[[Category: nucleotide-binding]]
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[[Category: Nucleotide-binding]]
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[[Category: peptide]]
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[[Category: Peptide]]
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[[Category: phosphoprotein]]
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[[Category: Phosphoprotein]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: substrate]]
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[[Category: Substrate]]
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[[Category: transducer]]
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[[Category: Transducer]]
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[[Category: transferase]]
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[[Category: Transferase]]
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[[Category: transmembrane]]
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[[Category: Transmembrane]]
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[[Category: tyrosine-protein kinase]]
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[[Category: Tyrosine-protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:06:11 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:28:57 2008''
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Revision as of 18:06, 4 May 2008

Image:3bu3.jpg

Template:STRUCTURE 3bu3

Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide


Contents

Overview

Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2.

Disease

Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]

About this Structure

3BU3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2., Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR, Nat Struct Mol Biol. 2008 Mar;15(3):251-8. Epub 2008 Feb 17. PMID:18278056 Page seeded by OCA on Sun May 4 21:06:11 2008

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