1y91

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{{Seed}}
 
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[[Image:1y91.png|left|200px]]
 
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==Crystal structure of human CDK2 complexed with a pyrazolo[1,5-a]pyrimidine inhibitor==
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The line below this paragraph, containing "STRUCTURE_1y91", creates the "Structure Box" on the page.
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<StructureSection load='1y91' size='340' side='right'caption='[[1y91]], [[Resolution|resolution]] 2.15&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'>[[1y91]] 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=1Y91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y91 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]] 2.15&#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=CT9:4-[5-(TRANS-4-AMINOCYCLOHEXYLAMINO)-3-ISOPROPYLPYRAZOLO[1,5-A]PYRIMIDIN-7-YLAMINO]-N,N-DIMETHYLBENZENESULFONAMIDE'>CT9</scene></td></tr>
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{{STRUCTURE_1y91| PDB=1y91 | 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=1y91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y91 OCA], [https://pdbe.org/1y91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y91 RCSB], [https://www.ebi.ac.uk/pdbsum/1y91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y91 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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== 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/y9/1y91_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=1y91 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 protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. Some examples were shown to inhibit the growth of human colon tumour cells, were equipotent for CDK1 and were selective against GSK-3beta and other kinases.
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===Crystal structure of human CDK2 complexed with a pyrazolo[1,5-a]pyrimidine inhibitor===
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Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2.,Williamson DS, Parratt MJ, Bower JF, Moore JD, Richardson CM, Dokurno P, Cansfield AD, Francis GL, Hebdon RJ, Howes R, Jackson PS, Lockie AM, Murray JB, Nunns CL, Powles J, Robertson A, Surgenor AE, Torrance CJ Bioorg Med Chem Lett. 2005 Feb 15;15(4):863-7. PMID:15686876<ref>PMID:15686876</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 1y91" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15686876}}, adds the Publication Abstract to the page
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*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15686876 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15686876}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1Y91 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=1Y91 OCA].
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==Reference==
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<ref group="xtra">PMID:15686876</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Bower, J F.]]
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[[Category: Bower JF]]
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[[Category: Cansfield, A D.]]
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[[Category: Cansfield AD]]
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[[Category: Dokurno, P.]]
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[[Category: Dokurno P]]
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[[Category: Francis, G L.]]
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[[Category: Francis GL]]
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[[Category: Hebdon, R J.]]
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[[Category: Hebdon RJ]]
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[[Category: Howes, R.]]
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[[Category: Howes R]]
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[[Category: Jackson, P S.]]
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[[Category: Jackson PS]]
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[[Category: Lockie, A M.]]
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[[Category: Lockie AM]]
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[[Category: Moore, J D.]]
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[[Category: Moore JD]]
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[[Category: Murray, J B.]]
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[[Category: Murray JB]]
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[[Category: Nunns, C L.]]
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[[Category: Nunns CL]]
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[[Category: Parratt, M J.]]
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[[Category: Parratt MJ]]
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[[Category: Powles, J.]]
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[[Category: Powles J]]
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[[Category: Richardson, C M.]]
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[[Category: Richardson CM]]
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[[Category: Robertson, A.]]
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[[Category: Robertson A]]
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[[Category: Surgenor, A E.]]
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[[Category: Surgenor AE]]
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[[Category: Torrance, C J.]]
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[[Category: Torrance CJ]]
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[[Category: Williamson, D S.]]
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[[Category: Williamson DS]]
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[[Category: Atp-binding]]
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[[Category: Cdk2]]
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[[Category: Cell cycle]]
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[[Category: Mitosis]]
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[[Category: Phosphorylation]]
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[[Category: Pyrazolopyrimidine inhibitor]]
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[[Category: Serine/threonine protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 10:13:16 2009''
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Current revision

Crystal structure of human CDK2 complexed with a pyrazolo[1,5-a]pyrimidine inhibitor

PDB ID 1y91

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