1qqg

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(New page: 200px<br /> <applet load="1qqg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qqg, resolution 2.3&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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[[Image:1qqg.gif|left|200px]]<br />
 
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<applet load="1qqg" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1qqg, resolution 2.3&Aring;" />
 
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'''CRYSTAL STRUCTURE OF THE PH-PTB TARGETING REGION OF IRS-1'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF THE PH-PTB TARGETING REGION OF IRS-1==
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We have determined the crystal structure at 2.3-A resolution of an, amino-terminal segment of human insulin receptor substrate 1 that, encompasses its pleckstrin homology (PH) and phosphotyrosine binding (PTB), domains. Both domains adopt the canonical seven-stranded beta-sandwich PH, domain fold. The domains are closely associated, with a 720-A(2) contact, surface buried between them that appears to be stabilized by ionic, hydrophobic, and hydrogen bonding interactions. The nonconserved, 46-residue linker between the domains is disordered. The PTB domain, peptide binding site is fully exposed on the molecular surface, as is a, large cationic patch at the base of the PH domain that is a likely binding, site for the head groups of phosphatidylinositol phosphates. Binding, assays confirm that phosphatidylinositol phosphates bind the PH domain, but not the PTB domain. Ligand binding to the PH domain does not alter PTB, domain interactions, and vice versa. The structural and accompanying, functional data illustrate how the two binding domains might act, cooperatively to effectively increase local insulin receptor substrate 1, concentration at the membrane and transiently fix the receptor and, substrate, to allow multiple phosphorylation reactions to occur during, each union.
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<StructureSection load='1qqg' size='340' side='right'caption='[[1qqg]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1qqg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QQG FirstGlance]. <br>
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Known diseases associated with this structure: Coronary artery disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147545 147545]], Diabetes mellitus, noninsulin-dependent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147545 147545]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qqg OCA], [https://pdbe.org/1qqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qqg RCSB], [https://www.ebi.ac.uk/pdbsum/1qqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qqg ProSAT]</span></td></tr>
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==About this Structure==
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</table>
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1QQG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QQG OCA].
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== Disease ==
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[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853].<ref>PMID:14707024</ref> <ref>PMID:8723689</ref> <ref>PMID:10206679</ref> <ref>PMID:12843189</ref> <ref>PMID:15590636</ref>
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==Reference==
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== Function ==
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Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1., Dhe-Paganon S, Ottinger EA, Nolte RT, Eck MJ, Shoelson SE, Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8378-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10411883 10411883]
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[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).<ref>PMID:16878150</ref> <ref>PMID:14707024</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qq/1qqg_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qqg ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Dhe-Paganon, S.]]
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[[Category: Dhe-Paganon S]]
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[[Category: Shoelson, S.E.]]
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[[Category: Shoelson SE]]
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[[Category: beta-sandwhich]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:55:32 2007''
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Current revision

CRYSTAL STRUCTURE OF THE PH-PTB TARGETING REGION OF IRS-1

PDB ID 1qqg

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