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1skj

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(New page: 200px<br /><applet load="1skj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1skj, resolution 2.0&Aring;" /> '''COCRYSTAL STRUCTURE O...)
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[[Image:1skj.gif|left|200px]]<br /><applet load="1skj" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1skj, resolution 2.0&Aring;" />
 
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'''COCRYSTAL STRUCTURE OF UREA-SUBSTITUTED PHOSPHOPEPTIDE COMPLEX'''<br />
 
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==Overview==
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==COCRYSTAL STRUCTURE OF UREA-SUBSTITUTED PHOSPHOPEPTIDE COMPLEX==
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The specific association of an SH2 domain with a phosphotyrosine, (pTyr)-containing sequence of another protein precipitates a cascade of, intracellular molecular interactions (signals) which effect a wide range, of intracellular processes. The nonreceptor tyrosine kinase Src, which has, been associated with breast cancer and osteoporosis, contains an SH2, domain. Inhibition of Src SH2-phosphoprotein interactions by small, molecules will aid biological proof-of-concept studies which may lead to, the development of novel therapeutic agents. Structure-based design, efforts have focused on reducing the size and charge of Src SH2 ligands, while increasing their ability to penetrate cells and reach the, intracellular Src SH2 domain target. In this report we describe the, synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.
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<StructureSection load='1skj' size='340' side='right'caption='[[1skj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1skj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SKJ FirstGlance]. <br>
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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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UR2:4-[3-CARBOXYMETHYL-3-(4-PHOSPHONOOXY-BENZYL)-UREIDO]-4-[(3-CYCLOHEXYL-PROPYL)-METHYL-CARBAMOYL]BUTYRIC+ACID'>UR2</scene></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=1skj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1skj OCA], [https://pdbe.org/1skj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1skj RCSB], [https://www.ebi.ac.uk/pdbsum/1skj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1skj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SRC_RSVSA SRC_RSVSA] This phosphoprotein, required for both the initiation and the maintenance of neoplastic transformation, is a protein kinase that catalyzes the phosphorylation of tyrosine residues in vitro.
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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/sk/1skj_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=1skj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The specific association of an SH2 domain with a phosphotyrosine (pTyr)-containing sequence of another protein precipitates a cascade of intracellular molecular interactions (signals) which effect a wide range of intracellular processes. The nonreceptor tyrosine kinase Src, which has been associated with breast cancer and osteoporosis, contains an SH2 domain. Inhibition of Src SH2-phosphoprotein interactions by small molecules will aid biological proof-of-concept studies which may lead to the development of novel therapeutic agents. Structure-based design efforts have focused on reducing the size and charge of Src SH2 ligands while increasing their ability to penetrate cells and reach the intracellular Src SH2 domain target. In this report we describe the synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.
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==About this Structure==
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Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand.,Plummer MS, Holland DR, Shahripour A, Lunney EA, Fergus JH, Marks JS, McConnell P, Mueller WT, Sawyer TK J Med Chem. 1997 Nov 7;40(23):3719-25. PMID:9371236<ref>PMID:9371236</ref>
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1SKJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus] with UR2 as [http://en.wikipedia.org/wiki/ligand ligand]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SKJ OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand., Plummer MS, Holland DR, Shahripour A, Lunney EA, Fergus JH, Marks JS, McConnell P, Mueller WT, Sawyer TK, J Med Chem. 1997 Nov 7;40(23):3719-25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9371236 9371236]
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</div>
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<div class="pdbe-citations 1skj" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rous sarcoma virus]]
[[Category: Rous sarcoma virus]]
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[[Category: Single protein]]
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[[Category: Holland DR]]
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[[Category: Transferase]]
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[[Category: Rubin JR]]
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[[Category: Holland, D.R.]]
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[[Category: Rubin, J.R.]]
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[[Category: UR2]]
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[[Category: peptidomimetic]]
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[[Category: phosphotyrosine recognition domain]]
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[[Category: pp60 src sh2 domain]]
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[[Category: tyrosine-protein kinase]]
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[[Category: ureido]]
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[[Category: v-src sh2 domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:26:23 2007''
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Current revision

COCRYSTAL STRUCTURE OF UREA-SUBSTITUTED PHOSPHOPEPTIDE COMPLEX

PDB ID 1skj

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