3ddp: Difference between revisions

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-[[Image:3ddp.png|left|200px]]
-{{STRUCTURE_3ddp|  PDB=3ddp  |  SCENE=  }}
+==Structure of phosphorylated Thr160 CDK2/cyclin A in complex with the inhibitor CR8==
+<StructureSection load='3ddp' size='340' side='right'caption='[[3ddp]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3ddp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDP 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]] 2.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RC8:(2R)-2-({9-(1-METHYLETHYL)-6-[(4-PYRIDIN-2-YLBENZYL)AMINO]-9H-PURIN-2-YL}AMINO)BUTAN-1-OL'>RC8</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=3ddp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ddp OCA], [https://pdbe.org/3ddp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ddp RCSB], [https://www.ebi.ac.uk/pdbsum/3ddp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ddp ProSAT]</span></td></tr>
+</table>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dd/3ddp_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ddp ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Among the ten pharmacological inhibitors of cyclin-dependent kinases (CDKs) currently in clinical trials, the purine roscovitine (CYC202, Seliciclib) is undergoing phase 2 trials against non-small-cell lung and nasopharyngeal cancers. An extensive medicinal chemistry study, designed to generate more potent analogues of roscovitine, led to the identification of an optimal substitution at the N6 position (compound CR8). An extensive selectivity study (108 kinases) highlights the exquisite selectivity of CR8 for CDK1/2/3/5/7/9. CR8 was 2- to 4-fold more potent than (R)-roscovitine at inhibiting these kinases. Cocrystal structures of (R)-CR8 and (R)-roscovitine with pCDK2/cyclin A showed that both inhibitors adopt essentially identical positions. The cellular effects of CR8 and (R)-roscovitine were investigated in human neuroblastoma SH-SY5Y cells. CR8 inhibited the phosphorylation of CDK1 and 9 substrates, with a 25-50 times higher potency compared to (R)-roscovitine. CR8 was consistently more potent than (R)-roscovitine at inducing apoptotic cell death parameters: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium reduction (40-fold), lactate dehydrogenase release (35-fold), caspases activation (68-fold) and poly-(ADP-ribose)polymerase cleavage (50-fold). This improved cell death-inducing activity of CR8 over (R)-roscovitine was observed in 25 different cell lines. Altogether these results show that second-generation analogues of (R)-roscovitine can be designed with improved antitumor potential.
-===Structure of phosphorylated Thr160 CDK2/cyclin A in complex with the inhibitor CR8===
+CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases.,Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H, Meijer L Oncogene. 2008 Oct 2;27(44):5797-807. Epub 2008 Jun 23. PMID:18574471<ref>PMID:18574471</ref>
-{{ABSTRACT_PUBMED_18574471}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3ddp" style="background-color:#fffaf0;"></div>
-[[3ddp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDP OCA].
 ==See Also==
-*[[Cell Division Protein Kinase 2|Cell Division Protein Kinase 2]]
+*[[Cyclin 3D structures|Cyclin 3D structures]]
-*[[Cyclin|Cyclin]]
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:018574471</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
-[[Category: Cyclin-dependent kinase]]
 [[Category: Homo sapiens]]
-[[Category: Echalier, A.]]
+[[Category: Large Structures]]
-[[Category: Endicott, J A.]]
+[[Category: Echalier A]]
-[[Category: Atp-binding]]
+[[Category: Endicott JA]]
-[[Category: Cell cycle]]
-[[Category: Cell division]]
-[[Category: Cyclin]]
-[[Category: Mitosis]]
-[[Category: Nucleotide-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Phosphorylation]]
-[[Category: Ser/thr protein kinase]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase-cell cycle complex]]