2aoa
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain== | |
| - | + | <StructureSection load='2aoa' size='340' side='right' caption='[[2aoa]], [[Resolution|resolution]] 1.99Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[2aoa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AOA FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=S1S:2-(4-((9S,10S,14S,Z)-18-(2-AMINO-2-OXOETHYL)-9-(CARBOXYMETHYL)-14-(NAPHTHALEN-1-YLMETHYL)-8,17,20-TRIOXO-7,16,19-TRIAZASPIRO[5.14]ICOS-11-EN-10-YL)PHENYL)MALONIC+ACID'>S1S</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2, ASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aoa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aoa RCSB], [http://www.ebi.ac.uk/pdbsum/2aoa PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ao/2aoa_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The high-affinity binding of the growth factor receptor-bound protein 2 (Grb2) SH2 domain to tyrosine-phosphorylated cytosolic domains of receptor tyrosine kinases (RTKs) is an attractive target for therapeutic intervention in many types of cancer. We report here two crystal forms of a complex between the Grb2 SH2 domain and a potent non-phosphorus-containing macrocyclic peptide mimetic that exhibits significant anti-proliferative effects against erbB-2-dependent breast cancers. This agent represents a "second generation" inhibitor with greatly improved binding affinity and bio-availability compared to its open-chain counterpart. The structures were determined at 2.0A and 1.8A with one and two domain-swapped dimers per asymmetric unit, respectively. The mode of binding and specific interactions between the protein and the inhibitor provide insight into the high potency of this class of macrocylic compounds and may aid in further optimization as part of the iterative rational drug design process. | ||
| - | + | Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain.,Phan J, Shi ZD, Burke TR Jr, Waugh DS J Mol Biol. 2005 Oct 14;353(1):104-15. PMID:16165154<ref>PMID:16165154</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]] | *[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Burke, T R.]] | [[Category: Burke, T R.]] | ||
Revision as of 01:15, 30 September 2014
Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain
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