3ddp: Difference between revisions

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-{{Seed}}
-[[Image:3ddp.jpg|left|200px]]
-<!--
+==Structure of phosphorylated Thr160 CDK2/cyclin A in complex with the inhibitor CR8==
-The line below this paragraph, containing "STRUCTURE_3ddp", creates the "Structure Box" on the page.
+<StructureSection load='3ddp' size='340' side='right'caption='[[3ddp]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</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>
-{{STRUCTURE_3ddp|  PDB=3ddp  |  SCENE=  }}
+<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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3ddp" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18574471}}, adds the Publication Abstract to the page
+*[[Cyclin 3D structures|Cyclin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18574471 is the PubMed ID number.
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_18574471}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-DDP is a [[Protein complex]] structure of sequences 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].
-==Reference==
-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 Jun 23;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18574471 18574471]
 [[Category: Bos taurus]]
-[[Category: Cyclin-dependent kinase]]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Echalier, A.]]
+[[Category: Echalier A]]
-[[Category: Endicott, J A.]]
+[[Category: Endicott JA]]
-[[Category: Atp-binding]]
-[[Category: Cell cycle]]
-[[Category: Cell division]]
-[[Category: Cyclin]]
-[[Category: Cytoplasm]]
-[[Category: Mitosis]]
-[[Category: Nucleotide-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Phosphorylation]]
-[[Category: Polymorphism]]
-[[Category: Ser/thr protein kinase]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase/cell cycle complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 23 11:52:10 2008''