4ueu
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Tyrosine kinase AS - a common ancestor of Src and Abl== | |
| + | <StructureSection load='4ueu' size='340' side='right'caption='[[4ueu]], [[Resolution|resolution]] 2.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ueu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4cds 4cds]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UEU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UEU FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ueu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ueu OCA], [https://pdbe.org/4ueu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ueu RCSB], [https://www.ebi.ac.uk/pdbsum/4ueu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ueu ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 4ueu" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: Kern | + | </StructureSection> |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Synthetic construct]] |
| - | [[Category: Zorba | + | [[Category: Agafonov RV]] |
| + | [[Category: Halpin JC]] | ||
| + | [[Category: Hoemberger MS]] | ||
| + | [[Category: Kern D]] | ||
| + | [[Category: Kutter S]] | ||
| + | [[Category: Theobald DL]] | ||
| + | [[Category: Wilson C]] | ||
| + | [[Category: Zorba A]] | ||
Current revision
Tyrosine kinase AS - a common ancestor of Src and Abl
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