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==The crystal structure of human abl1 kinase domain in complex with ABL1-A11== | ==The crystal structure of human abl1 kinase domain in complex with ABL1-A11== | ||
<StructureSection load='7w7x' size='340' side='right'caption='[[7w7x]]' scene=''> | <StructureSection load='7w7x' size='340' side='right'caption='[[7w7x]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W7X FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W7X FirstGlance]. <br> | ||
</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=7w7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w7x OCA], [https://pdbe.org/7w7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w7x RCSB], [https://www.ebi.ac.uk/pdbsum/7w7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w7x ProSAT]</span></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]] 2.0000093Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8DW:5-[5-(dimethylcarbamoyl)pyridin-3-yl]-3-(5-fluorosulfonyloxy-2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine'>8DW</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=7w7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w7x OCA], [https://pdbe.org/7w7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w7x RCSB], [https://www.ebi.ac.uk/pdbsum/7w7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w7x ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite recent interests in developing lysine-targeting covalent inhibitors, no general approach is available to create such compounds. We report herein a general approach to develop cell-active covalent inhibitors of protein kinases by targeting the conserved catalytic lysine residue using key SuFEx and salicylaldehyde-based imine chemistries. We validated the strategy by successfully developing (irreversible and reversible) covalent inhibitors against BCR-ABL kinase. Our lead compounds showed high levels of selectivity in biochemical assays, exhibited nanomolar potency against endogenous ABL kinase in cellular assays, and were active against most drug-resistant ABL mutations. Among them, the salicylaldehyde-containing A5 is the first-ever reversible covalent ABL inhibitor that possessed time-dependent ABL inhibition with prolonged residence time and few cellular off-targets in K562 cells. Bioinformatics further suggested the generality of our strategy against the human kinome. | |||
Cell-Active, Reversible, and Irreversible Covalent Inhibitors that Selectively Target the Catalytic Lysine of BCR-ABL Kinase.,Chen P, Sun J, Zhu C, Tang G, Wang W, Xu M, Xiang M, Zhang C, Zhang ZM, Gao L, Yao SQ Angew Chem Int Ed Engl. 2022 Apr 19. doi: 10.1002/anie.202203878. PMID:35438229<ref>PMID:35438229</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7w7x" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] | *[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||