7fic
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7fic]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FIC FirstGlance]. <br> | <table><tr><td colspan='2'>[[7fic]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FIC FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5YZ:6-[(5-cyclopropyl-1~{H}-pyrazol-3-yl)amino]-2-[4-[(3-methyl-4-oxidanyl-phenyl)methyl]piperazin-1-yl]-~{N}-prop-2-ynyl-pyrimidine-4-carboxamide'>5YZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.32Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5YZ:6-[(5-cyclopropyl-1~{H}-pyrazol-3-yl)amino]-2-[4-[(3-methyl-4-oxidanyl-phenyl)methyl]piperazin-1-yl]-~{N}-prop-2-ynyl-pyrimidine-4-carboxamide'>5YZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7fic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fic OCA], [https://pdbe.org/7fic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fic RCSB], [https://www.ebi.ac.uk/pdbsum/7fic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fic ProSAT]</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=7fic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fic OCA], [https://pdbe.org/7fic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fic RCSB], [https://www.ebi.ac.uk/pdbsum/7fic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fic ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == | + | <div style="background-color:#fffaf0;"> |
| - | + | == Publication Abstract from PubMed == | |
| + | The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles beyond cysteine. Although the conserved catalytic lysine in protein kinases is an attractive candidate for a covalent approach, selectivity remains an obvious challenge. Moreover, few covalent inhibitors have been shown to engage the kinase catalytic lysine in animals. We hypothesized that reversible, lysine-targeted inhibitors could provide sustained kinase engagement in vivo, with selectivity driven in part by differences in residence time. By strategically linking benzaldehydes to a promiscuous kinase binding scaffold, we developed chemoproteomic probes that reversibly and covalently engage >200 protein kinases in cells and mice. Probe-kinase residence time was dramatically enhanced by a hydroxyl group ortho to the aldehyde. Remarkably, only a few kinases, including Aurora A, showed sustained, quasi-irreversible occupancy in vivo, the structural basis for which was revealed by X-ray crystallography. We anticipate broad application of salicylaldehyde-based probes to proteins that lack a druggable cysteine. | ||
| + | |||
| + | Reversible lysine-targeted probes reveal residence time-based kinase selectivity.,Yang T, Cuesta A, Wan X, Craven GB, Hirakawa B, Khamphavong P, May JR, Kath JC, Lapek JD Jr, Niessen S, Burlingame AL, Carelli JD, Taunton J Nat Chem Biol. 2022 Sep;18(9):934-941. doi: 10.1038/s41589-022-01019-1. Epub 2022 , May 19. PMID:35590003<ref>PMID:35590003</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7fic" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Reversible lysine-targeted probes reveal residence time-based kinase selectivity in vivo
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