This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
4ueu
From Proteopedia
(Difference between revisions)
| (4 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| + | |||
==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]] 2.95Å' scene=''> | + | <StructureSection load='4ueu' size='340' side='right'caption='[[4ueu]], [[Resolution|resolution]] 2.95Å' 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 [ | + | <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=' | + | </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=' | + | <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'>[ | + | <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®/PubMed®, 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: | + | [[Category: Large Structures]] |
| - | [[Category: Agafonov | + | [[Category: Synthetic construct]] |
| - | [[Category: Halpin | + | [[Category: Agafonov RV]] |
| - | [[Category: Hoemberger | + | [[Category: Halpin JC]] |
| - | [[Category: Kern | + | [[Category: Hoemberger MS]] |
| - | [[Category: Kutter | + | [[Category: Kern D]] |
| - | [[Category: Theobald | + | [[Category: Kutter S]] |
| - | [[Category: Wilson | + | [[Category: Theobald DL]] |
| - | [[Category: Zorba | + | [[Category: Wilson C]] |
| - | + | [[Category: Zorba A]] | |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Tyrosine kinase AS - a common ancestor of Src and Abl
| |||||||||||
