2w05: Difference between revisions

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{{Seed}}
[[Image:2w05.png|left|200px]]


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==Structure of CDK2 in complex with an imidazolyl pyrimidine, compound 5b==
The line below this paragraph, containing "STRUCTURE_2w05", creates the "Structure Box" on the page.
<StructureSection load='2w05' size='340' side='right'caption='[[2w05]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2w05]] is a 1 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=2W05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W05 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]] 1.9&#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=FRT:N-(2-METHOXYETHYL)-4-({4-[2-METHYL-1-(1-METHYLETHYL)-1H-IMIDAZOL-5-YL]PYRIMIDIN-2-YL}AMINO)BENZENESULFONAMIDE'>FRT</scene></td></tr>
{{STRUCTURE_2w05| PDB=2w05 |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w05 OCA], [https://pdbe.org/2w05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w05 RCSB], [https://www.ebi.ac.uk/pdbsum/2w05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w05 ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== 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/w0/2w05_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2w05 ConSurf].
<div style="clear:both"></div>


===STRUCTURE OF CDK2 IN COMPLEX WITH AN IMIDAZOLYL PYRIMIDINE, COMPOUND 5B===
==See Also==
 
*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
 
== References ==
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{{ABSTRACT_PUBMED_18815031}}
 
==About this Structure==
2W05 is a 1 chain structure of sequence 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=2W05 OCA].
 
==Reference==
<ref group="xtra">PMID:18815031</ref><references group="xtra"/>
[[Category: Cyclin-dependent kinase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Anderson, M.]]
[[Category: Large Structures]]
[[Category: Andrews, D M.]]
[[Category: Anderson M]]
[[Category: Barker, A J.]]
[[Category: Andrews DM]]
[[Category: Brassington, C A.]]
[[Category: Barker AJ]]
[[Category: Breed, J.]]
[[Category: Brassington CA]]
[[Category: Byth, K F.]]
[[Category: Breed J]]
[[Category: Culshaw, J D.]]
[[Category: Byth KF]]
[[Category: Finlay, M R.]]
[[Category: Culshaw JD]]
[[Category: Fisher, E.]]
[[Category: Finlay MR]]
[[Category: Green, C P.]]
[[Category: Fisher E]]
[[Category: Heaton, D W.]]
[[Category: Green CP]]
[[Category: Nash, I A.]]
[[Category: Heaton DW]]
[[Category: Newcombe, N J.]]
[[Category: Nash IA]]
[[Category: Oakes, S E.]]
[[Category: Newcombe NJ]]
[[Category: Pauptit, R A.]]
[[Category: Oakes SE]]
[[Category: Roberts, A.]]
[[Category: Pauptit RA]]
[[Category: Stanway, J J.]]
[[Category: Roberts A]]
[[Category: Thomas, A P.]]
[[Category: Stanway JJ]]
[[Category: Tucker, J A.]]
[[Category: Thomas AP]]
[[Category: Weir, H M.]]
[[Category: Tucker JA]]
[[Category: Atp-binding]]
[[Category: Weir HM]]
[[Category: Cell cycle]]
[[Category: Cell division]]
[[Category: Kinase]]
[[Category: Mitosis]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Phosphorylation]]
[[Category: Polymorphism]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 02:37:37 2009''