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2w96

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{{Seed}}
 
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[[Image:2w96.jpg|left|200px]]
 
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==Crystal Structure of CDK4 in complex with a D-type cyclin==
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The line below this paragraph, containing "STRUCTURE_2w96", creates the "Structure Box" on the page.
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<StructureSection load='2w96' size='340' side='right'caption='[[2w96]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2w96]] is a 2 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=2W96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W96 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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{{STRUCTURE_2w96| PDB=2w96 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w96 OCA], [https://pdbe.org/2w96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w96 RCSB], [https://www.ebi.ac.uk/pdbsum/2w96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w96 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CDK4_HUMAN CDK4_HUMAN] Defects in CDK4 are a cause of susceptibility to cutaneous malignant melanoma type 3 (CMM3) [MIM:[https://omim.org/entry/609048 609048]. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.<ref>PMID:7652577</ref> <ref>PMID:8528263</ref> <ref>PMID:9311594</ref> <ref>PMID:9425228</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CDK4_HUMAN CDK4_HUMAN] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.<ref>PMID:9003781</ref> <ref>PMID:15241418</ref> <ref>PMID:18827403</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w9/2w96_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2w96 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. Among the cyclin/CDKs, CDK4 and cyclin D1 are the most frequently activated by somatic genetic alterations in multiple tumor types. Thus, aberrant regulation of the CDK4/cyclin D1 pathway plays an essential role in oncogenesis; hence, CDK4 is a genetically validated therapeutic target. Although X-ray crystallographic structures have been determined for various CDK/cyclin complexes, CDK4/cyclin D1 has remained highly refractory to structure determination. Here, we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A. Although CDK4 is bound to cyclin D1 and has a phosphorylated T-loop, CDK4 is in an inactive conformation and the conformation of the heterodimer diverges from the previously known CDK/cyclin binary complexes, which suggests a unique mechanism for the process of CDK4 regulation and activation.
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===CRYSTAL STRUCTURE OF CDK4 IN COMPLEX WITH A D-TYPE CYCLIN===
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Crystal structure of human CDK4 in complex with a D-type cyclin.,Day PJ, Cleasby A, Tickle IJ, O'Reilly M, Coyle JE, Holding FP, McMenamin RL, Yon J, Chopra R, Lengauer C, Jhoti H Proc Natl Acad Sci U S A. 2009 Feb 23. PMID:19237565<ref>PMID:19237565</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2w96" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19237565}}, adds the Publication Abstract to the page
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*[[Cyclin 3D structures|Cyclin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19237565 is the PubMed ID number.
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*[[Cyclin Dependent Kinase-4|Cyclin Dependent Kinase-4]]
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*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
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{{ABSTRACT_PUBMED_19237565}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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2W96 is a 2 chains structure of sequences 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=2W96 OCA].
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:19237565</ref><references group="xtra"/>
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[[Category: Cyclin-dependent kinase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Chopra, R.]]
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[[Category: Large Structures]]
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[[Category: Cleasby, A.]]
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[[Category: Chopra R]]
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[[Category: Coyle, J E.]]
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[[Category: Cleasby A]]
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[[Category: Day, P J.]]
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[[Category: Coyle JE]]
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[[Category: Holding, F P.]]
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[[Category: Day PJ]]
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[[Category: Jhoti, H.]]
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[[Category: Holding FP]]
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[[Category: Lengauer, C.]]
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[[Category: Jhoti H]]
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[[Category: Mcmenamin, R L.]]
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[[Category: Lengauer C]]
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[[Category: Reilly, M O.]]
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[[Category: McMenamin RL]]
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[[Category: Tickle, I J.]]
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[[Category: Reilly MO]]
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[[Category: Yon, J.]]
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[[Category: Tickle IJ]]
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[[Category: Atp-binding]]
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[[Category: Yon J]]
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[[Category: Cell cycle]]
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[[Category: Cell division]]
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[[Category: Chromosomal rearrangement]]
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[[Category: Cyclin]]
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[[Category: Cyclin dependent kinase]]
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[[Category: Disease mutation]]
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[[Category: Drug desgn]]
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[[Category: Kinase]]
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[[Category: Nucleotide-binding]]
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[[Category: Oncology]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Proto-oncogene]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 11 11:18:05 2009''
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Current revision

Crystal Structure of CDK4 in complex with a D-type cyclin

PDB ID 2w96

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