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4csv

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'''Unreleased structure'''
 
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The entry 4csv is ON HOLD
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==Tyrosine kinase AS - a common ancestor of Src and Abl bound to Gleevec==
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<StructureSection load='4csv' size='340' side='right'caption='[[4csv]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4csv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CSV 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]] 2.05&#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=STI:4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE'>STI</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=4csv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4csv OCA], [https://pdbe.org/4csv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4csv RCSB], [https://www.ebi.ac.uk/pdbsum/4csv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4csv ProSAT]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Macromolecular function is rooted in energy landscapes, where sequence determines not a single structure but an ensemble of conformations. Hence, evolution modifies a protein's function by altering its energy landscape. Here, we recreate the evolutionary pathway between two modern human oncogenes, Src and Abl, by reconstructing their common ancestors. Our evolutionary reconstruction combined with x-ray structures of the common ancestor and pre-steady-state kinetics reveals a detailed atomistic mechanism for selectivity of the successful cancer drug Gleevec. Gleevec affinity is gained during the evolutionary trajectory toward Abl and lost toward Src, primarily by shifting an induced-fit equilibrium that is also disrupted in the clinical T315I resistance mutation. This work reveals the mechanism of Gleevec specificity while offering insights into how energy landscapes evolve.
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Authors: Kutter, S., Wilson, C., Cruz, L., Agafonov, R.V., Hoemberger, M.S., Zorba, A., Kern, D.
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Kinase dynamics. Using ancient protein kinases to unravel a modern cancer drug's mechanism.,Wilson C, Agafonov RV, Hoemberger M, Kutter S, Zorba A, Halpin J, Buosi V, Otten R, Waterman D, Theobald DL, Kern D Science. 2015 Feb 20;347(6224):882-6. doi: 10.1126/science.aaa1823. PMID:25700521<ref>PMID:25700521</ref>
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Description: Tyrosine kinase AS -a common ancestor of Src and Abl bound to Gleevec
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4csv" 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]]
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[[Category: Synthetic construct]]
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[[Category: Agafonov RV]]
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[[Category: Cruz L]]
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[[Category: Hoemberger MS]]
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[[Category: Kern D]]
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[[Category: Kutter S]]
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[[Category: Wilson C]]
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[[Category: Zorba A]]

Current revision

Tyrosine kinase AS - a common ancestor of Src and Abl bound to Gleevec

PDB ID 4csv

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