3tnw

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[[Image:3tnw.jpg|left|200px]]
 
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==Structure of CDK2/cyclin A in complex with CAN508==
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<StructureSection load='3tnw' size='340' side='right'caption='[[3tnw]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3tnw]] 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=3TNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TNW 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&#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=F18:4-[(E)-(3,5-DIAMINO-1H-PYRAZOL-4-YL)DIAZENYL]PHENOL'>F18</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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{{STRUCTURE_3tnw| PDB=3tnw | 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=3tnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tnw OCA], [https://pdbe.org/3tnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tnw RCSB], [https://www.ebi.ac.uk/pdbsum/3tnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tnw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CDK2_HUMAN CDK2_HUMAN] Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.<ref>PMID:10499802</ref> <ref>PMID:11051553</ref> <ref>PMID:10995386</ref> <ref>PMID:10995387</ref> <ref>PMID:10884347</ref> <ref>PMID:11113184</ref> <ref>PMID:15800615</ref> <ref>PMID:18372919</ref> <ref>PMID:20147522</ref> <ref>PMID:20079829</ref> <ref>PMID:20935635</ref> <ref>PMID:20195506</ref> <ref>PMID:19966300</ref> <ref>PMID:21262353</ref> <ref>PMID:21596315</ref> <ref>PMID:21319273</ref> <ref>PMID:17495531</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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CDK9 is the kinase of positive transcription elongation factor b and facilitates the transition of paused RNA polymerase II to processive transcription elongation. CDK9 is a validated target for the treatment of cancer, cardiac hypertrophy, and human immunodeficiency virus. Here we analyze different CDK9/cyclin T variants to identify a form of the complex amenable to use in inhibitor design. To demonstrate the utility of this system, we have determined the crystal structures of CDK9/cyclin T and CDK2/cyclin A bound to the CDK9-specific inhibitor CAN508. Comparison of the structures reveals CDK9-specific conformational changes and identifies a CDK9-specific hydrophobic pocket, adjacent to the alphaC-helix. By comparison with a previously published structure of CDK9/cyclin T/human immunodeficiency virus TAT we find that the CDK9 alphaC-helix has a degree of conformational variability that has the potential to be exploited for inhibitor design.
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===Structure of CDK2/cyclin A in complex with CAN508===
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The CDK9 C-helix Exhibits Conformational Plasticity That May Explain the Selectivity of CAN508.,Baumli S, Hole AJ, Noble ME, Endicott JA ACS Chem Biol. 2012 Feb 10. PMID:22292676<ref>PMID:22292676</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 3tnw" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_22292676}}, 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 22292676 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_22292676}}
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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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[[3tnw]] 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=3TNW OCA].
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==Reference==
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<ref group="xtra">PMID:022292676</ref><references group="xtra"/>
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Cyclin-dependent kinase]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Baumli, S.]]
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[[Category: Large Structures]]
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[[Category: Endicott, J A.]]
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[[Category: Baumli S]]
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[[Category: Hole, A J.]]
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[[Category: Endicott JA]]
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[[Category: Cyclin some]]
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[[Category: Hole AJ]]
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[[Category: Cyclin dependent kinase]]
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[[Category: Kinase cyclin]]
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[[Category: Phosphorylation at cdk2 threonine 160]]
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[[Category: Phosphotransferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Structure of CDK2/cyclin A in complex with CAN508

PDB ID 3tnw

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