3pxf: Difference between revisions
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[[ | ==CDK2 in complex with two molecules of 8-anilino-1-naphthalene sulfonate== | ||
<StructureSection load='3pxf' size='340' side='right' caption='[[3pxf]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pxf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PXF FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2AN:8-ANILINO-1-NAPHTHALENE+SULFONATE'>2AN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pxq|3pxq]], [[3pxr|3pxr]], [[3pxy|3pxy]], [[3pxz|3pxz]], [[3py0|3py0]], [[3py1|3py1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pxf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pxf RCSB], [http://www.ebi.ac.uk/pdbsum/3pxf PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cyclin-dependent kinases (CDKs) are key regulatory enzymes in cell cycle progression and transcription. Aberrant activity of CDKs has been implicated in a number of medical conditions, and numerous small molecule CDK inhibitors have been reported as potential drug leads. However, these inhibitors exclusively bind to the ATP site, which is largely conserved among protein kinases, and clinical trials have not resulted in viable drug candidates, attributed in part to the lack of target selectivity. CDKs are unique among protein kinases, as their functionality strictly depends on association with their partner proteins, the cyclins. In an effort to identify potential target sites for disruption of the CDK-cyclin interaction, we probed the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS) with human CDK2 and cyclin A using fluorescence spectroscopy and protein crystallography. ANS interacts with free CDK2 in a saturation-dependent manner with an apparent Kd of 37 microM, and cyclin A displaced ANS from CDK2 with an EC50 value of 0.6 microM. Co-crystal structures with ANS alone and in ternary complex with ATP site-directed inhibitors revealed two ANS molecules bound adjacent to one another, away from the ATP site, in a large pocket that extends from the DFG region above the C-helix. Binding of ANS is accompanied by substantial structural changes in CDK2, resulting in a C-helix conformation that is incompatible for cyclin A association. These findings indicate the potential of the ANS binding pocket as a new target site for allosteric inhibitors disrupting the interaction of CDKs and cyclins. | |||
Discovery of a potential allosteric ligand binding site in CDK2.,Betzi S, Alam R, Martin MP, Lubbers DJ, Han H, Jakkaraj SR, Georg GI, Schonbrunn E ACS Chem Biol. 2011 Feb 3. PMID:21291269<ref>PMID:21291269</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Cell | *[[Cell division protein kinase 2|Cell division protein kinase 2]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Cyclin-dependent kinase]] | [[Category: Cyclin-dependent kinase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Alam, R | [[Category: Alam, R]] | ||
[[Category: Betzi, S | [[Category: Betzi, S]] | ||
[[Category: Schonbrunn, E | [[Category: Schonbrunn, E]] | ||
[[Category: Allosteric ligand]] | [[Category: Allosteric ligand]] | ||
[[Category: Protein kinase]] | [[Category: Protein kinase]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||