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| ==Crystal structure of the cdk2 in complex with oxindole inhibitor== | | ==Crystal structure of the cdk2 in complex with oxindole inhibitor== |
| <StructureSection load='4fkt' size='340' side='right' caption='[[4fkt]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='4fkt' size='340' side='right'caption='[[4fkt]], [[Resolution|resolution]] 1.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4fkt]] is a 1 chain structure with 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=4FKT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FKT FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4fkt]] 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=4FKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FKT FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=48K:N-[2-(DIMETHYLAMINO)ETHYL]-4-{[(Z)-(2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE'>48K</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=48K:N-[2-(DIMETHYLAMINO)ETHYL]-4-{[(Z)-(2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE'>48K</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ek3|4ek3]], [[4ek4|4ek4]], [[4ek5|4ek5]], [[4ek6|4ek6]], [[4ek8|4ek8]], [[4fkg|4fkg]], [[4fki|4fki]], [[4fkj|4fkj]], [[4fkl|4fkl]], [[4fko|4fko]], [[4fkp|4fkp]], [[4fkq|4fkq]], [[4fkr|4fkr]], [[4fks|4fks]], [[4fku|4fku]], [[4fkv|4fkv]], [[4fkw|4fkw]]</td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4fkt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fkt OCA], [https://pdbe.org/4fkt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fkt RCSB], [https://www.ebi.ac.uk/pdbsum/4fkt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fkt ProSAT]</span></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDK2, CDKN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4fkt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fkt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fkt RCSB], [http://www.ebi.ac.uk/pdbsum/4fkt PDBsum]</span></td></tr> | |
| </table> | | </table> |
| == 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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| ==See Also== | | ==See Also== |
| *[[Cell division protein kinase 2|Cell division protein kinase 2]] | | *[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Cyclin-dependent kinase]]
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| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Kang, Y N]] | | [[Category: Large Structures]] |
| [[Category: Stuckey, J A]] | | [[Category: Kang YN]] |
| [[Category: Transferase-transferase inhibitor complex]] | | [[Category: Stuckey JA]] |