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==Tyrosine kinase AS - a common ancestor of Src and Abl==
==Tyrosine kinase AS - a common ancestor of Src and Abl==
<StructureSection load='4ueu' size='340' side='right' caption='[[4ueu]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
<StructureSection load='4ueu' size='340' side='right'caption='[[4ueu]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ueu]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UEU FirstGlance]. <br>
<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ueu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ueu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ueu RCSB], [http://www.ebi.ac.uk/pdbsum/4ueu PDBsum]</span></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>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ueu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Large Structures]]
[[Category: Agafonov, R V]]
[[Category: Synthetic construct]]
[[Category: Halpin, J C]]
[[Category: Agafonov RV]]
[[Category: Hoemberger, M S]]
[[Category: Halpin JC]]
[[Category: Kern, D]]
[[Category: Hoemberger MS]]
[[Category: Kutter, S]]
[[Category: Kern D]]
[[Category: Theobald, D L]]
[[Category: Kutter S]]
[[Category: Wilson, C]]
[[Category: Theobald DL]]
[[Category: Zorba, A]]
[[Category: Wilson C]]
[[Category: Amppcp]]
[[Category: Zorba A]]
[[Category: Ancestor protein]]
[[Category: Dfg-in]]
[[Category: Transferase]]
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