2w9f

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{{Seed}}
 
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[[Image:2w9f.png|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_2w9f", creates the "Structure Box" on the page.
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<StructureSection load='2w9f' size='340' side='right'caption='[[2w9f]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
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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'>[[2w9f]] 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=2W9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W9F FirstGlance]. <br>
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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]] 2.85&#8491;</td></tr>
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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=2w9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w9f OCA], [https://pdbe.org/2w9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w9f RCSB], [https://www.ebi.ac.uk/pdbsum/2w9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w9f ProSAT]</span></td></tr>
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{{STRUCTURE_2w9f| PDB=2w9f | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CCND1_HUMAN CCND1_HUMAN] Note=A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle. Note=A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer. Defects in CCND1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving CCND1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus.
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== Function ==
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[https://www.uniprot.org/uniprot/CCND1_HUMAN CCND1_HUMAN] Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex 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 substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.<ref>PMID:9106657</ref> <ref>PMID:15241418</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/w9/2w9f_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=2w9f 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 2w9f" 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 3D structures|Cyclin-dependent kinase 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_19237565}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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2W9F 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=2W9F OCA].
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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 Thu Apr 2 16:20:59 2009''
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Current revision

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

PDB ID 2w9f

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