View source for 8p77


==Cryo-EM structure of CAK in complex with inhibitor ICEC0943==
<StructureSection load='8p77' size='340' side='right'caption='[[8p77]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8p77]] is a 3 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=8P77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P77 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=I73:(3S,4S)-4-[[[7-[(PHENYLMETHYL)AMINO]-3-PROPAN-2-YL-PYRAZOLO[1,5-A]PYRIMIDIN-5-YL]AMINO]METHYL]PIPERIDIN-3-OL'>I73</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=8p77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p77 OCA], [https://pdbe.org/8p77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p77 RCSB], [https://www.ebi.ac.uk/pdbsum/8p77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p77 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rational design of next-generation therapeutics can be facilitated by high-resolution structures of drug targets bound to small-molecule inhibitors. However, application of structure-based methods to macromolecules refractory to crystallization has been hampered by the often-limiting resolution and throughput of cryogenic electron microscopy (cryo-EM). Here, we use high-resolution cryo-EM to determine structures of the CDK-activating kinase, a master regulator of cell growth and division, in its free and nucleotide-bound states and in complex with 15 inhibitors at up to 1.8 A resolution. Our structures provide detailed insight into inhibitor interactions and networks of water molecules in the active site of cyclin-dependent kinase 7 and provide insights into the mechanisms contributing to inhibitor selectivity, thereby providing the basis for rational design of next-generation therapeutics. These results establish a methodological framework for the use of high-resolution cryo-EM in structure-based drug design.

High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design.,Cushing VI, Koh AF, Feng J, Jurgaityte K, Bondke A, Kroll SHB, Barbazanges M, Scheiper B, Bahl AK, Barrett AGM, Ali S, Kotecha A, Greber BJ Nat Commun. 2024 Mar 13;15(1):2265. doi: 10.1038/s41467-024-46375-9. PMID:38480681<ref>PMID:38480681</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8p77" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ali S]]
[[Category: Bahl AK]]
[[Category: Cushing VI]]
[[Category: Feng J]]
[[Category: Greber BJ]]
[[Category: Jurgaityte K]]
[[Category: Koh AF]]
[[Category: Kotecha A]]