5mhq

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'''Unreleased structure'''
 
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The entry 5mhq is ON HOLD
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==CCT068127 in complex with CDK2==
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<StructureSection load='5mhq' size='340' side='right' caption='[[5mhq]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
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Authors:
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5mhq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MHQ FirstGlance]. <br>
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Description:
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8QT:(2~{R},3~{S})-3-[[9-propan-2-yl-6-(pyridin-3-ylmethylamino)purin-2-yl]amino]pentan-2-ol'>8QT</scene></td></tr>
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[[Category: Unreleased Structures]]
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mhq OCA], [http://pdbe.org/5mhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mhq RCSB], [http://www.ebi.ac.uk/pdbsum/5mhq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mhq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://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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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Cyclin-dependent kinase]]
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[[Category: Barlow, C]]
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[[Category: Barrie, E]]
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[[Category: Blagg, J]]
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[[Category: Brown, N]]
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[[Category: Clarke, P]]
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[[Category: Garrett, M D]]
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[[Category: MacDonald, E]]
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[[Category: Mancusi, C]]
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[[Category: Martin, M P]]
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[[Category: Noble, M E.M]]
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[[Category: Poele, R te]]
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[[Category: Sharp, S]]
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[[Category: Wagner, S]]
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[[Category: Walton, M I]]
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[[Category: Whittaker, S R]]
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[[Category: Wilson, S]]
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[[Category: Workman, P]]
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[[Category: Cdk2]]
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[[Category: Cdk9]]
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[[Category: Cell cycle]]
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[[Category: Cell cycle-inhibitor complex]]
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[[Category: Inhibitor]]

Revision as of 06:08, 20 December 2017

CCT068127 in complex with CDK2

5mhq, resolution 1.30Å

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