View source for 4bcn


==Structure of CDK2 in complex with cyclin A and a 2-amino-4-heteroaryl- pyrimidine inhibitor==
<StructureSection load='4bcn' size='340' side='right'caption='[[4bcn]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bcn]] is a 4 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=4BCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BCN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T9N:2-[(3-HYDROXYPHENYL)AMINO]-4-[4-METHYL-2-(METHYLAMINO)-1,3-THIAZOL-5-YL]PYRIMIDINE-5-CARBONITRILE'>T9N</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=4bcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bcn OCA], [https://pdbe.org/4bcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bcn RCSB], [https://www.ebi.ac.uk/pdbsum/4bcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bcn ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclin-dependent kinase 9/cyclin T, the protein kinase heterodimer that constitutes positive transcription elongation factor b, is a well-validated target for treatment of several diseases, including cancer and cardiac hypertrophy. In order to aid inhibitor design and rationalise the basis for CDK9 selectivity, we have studied the CDK-binding properties of six different members of a 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile series that bind to both CDK9/cyclin T and CDK2/cyclin A. We find that for a given CDK, the melting temperature of a CDK/cyclin/inhibitor complex correlates well with inhibitor potency, suggesting that differential scanning fluorimetry (DSF) is a useful orthogonal measure of inhibitory activity for this series. We have used DSF to demonstrate that the binding of these compounds is independent of the presence or absence of the C-terminal tail region of CDK9, unlike the binding of the CDK9-selective inhibitor 5,6-dichlorobenzimida- zone-1-beta-D-ribofuranoside (DRB). Finally, based on 11 co-crystal structures bound to CDK9/cyclin T or CDK2/cyclin A, we conclude that selective inhibition of CDK9/cyclin T by members of the 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile series results from the relative malleability of the CDK9 active site, rather than from the formation of specific polar contacts.

Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity.,Hole A, Baumli S, Shao H, Shi S, Pepper C, Fischer PM, Wang S, Endicott JA, Noble M J Med Chem. 2012 Dec 20. PMID:23252711<ref>PMID:23252711</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bcn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclin 3D structures|Cyclin 3D structures]]
*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baumli S]]
[[Category: Endicott JA]]
[[Category: Hole AJ]]
[[Category: Noble MEM]]
[[Category: Wang S]]