2w1h: Difference between revisions

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<StructureSection load='2w1h' size='340' side='right'caption='[[2w1h]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
<StructureSection load='2w1h' size='340' side='right'caption='[[2w1h]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2w1h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2W1H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2W1H FirstGlance]. <br>
<table><tr><td colspan='2'>[[2w1h]] 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=2W1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W1H FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L0F:N-[3-(1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL]BENZAMIDE'>L0F</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]] 2.15&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1h08|1h08]], [[1pye|1pye]], [[2vth|2vth]], [[1v1k|1v1k]], [[2b53|2b53]], [[1h25|1h25]], [[1okv|1okv]], [[1ke7|1ke7]], [[1pxk|1pxk]], [[2bhh|2bhh]], [[2vta|2vta]], [[2uue|2uue]], [[1gz8|1gz8]], [[1e1v|1e1v]], [[1ol2|1ol2]], [[1h27|1h27]], [[1jsv|1jsv]], [[2b52|2b52]], [[1ke5|1ke5]], [[1fin|1fin]], [[2c5o|2c5o]], [[2c68|2c68]], [[1p2a|1p2a]], [[2vtt|2vtt]], [[2vtq|2vtq]], [[2c4g|2c4g]], [[1w0x|1w0x]], [[1h1q|1h1q]], [[2w05|2w05]], [[1pxo|1pxo]], [[1ke9|1ke9]], [[1hck|1hck]], [[2a0c|2a0c]], [[1jsu|1jsu]], [[1pxn|1pxn]], [[2uze|2uze]], [[2vtm|2vtm]], [[2v0d|2v0d]], [[1oiq|1oiq]], [[1h1r|1h1r]], [[2iw8|2iw8]], [[1gih|1gih]], [[1hcl|1hcl]], [[1pw2|1pw2]], [[2w06|2w06]], [[2vtn|2vtn]], [[1jst|1jst]], [[1oiu|1oiu]], [[1pxm|1pxm]], [[1b38|1b38]], [[1fq1|1fq1]], [[1vyw|1vyw]], [[1h1p|1h1p]], [[2c69|2c69]], [[1urc|1urc]], [[1pxi|1pxi]], [[2c6i|2c6i]], [[1ykr|1ykr]], [[2w17|2w17]], [[2uzd|2uzd]], [[2c5y|2c5y]], [[2c6k|2c6k]], [[1wcc|1wcc]], [[2j9m|2j9m]], [[1vyz|1vyz]], [[2vti|2vti]], [[1jvp|1jvp]], [[1w98|1w98]], [[1pkd|1pkd]], [[1p5e|1p5e]], [[2vts|2vts]], [[2c5p|2c5p]], [[2uzn|2uzn]], [[2b54|2b54]], [[1ke6|1ke6]], [[1pxj|1pxj]], [[2uzl|2uzl]], [[2cci|2cci]], [[2bkz|2bkz]], [[2g9x|2g9x]], [[1y91|1y91]], [[2iw6|2iw6]], [[1gij|1gij]], [[1r78|1r78]], [[1h0v|1h0v]], [[2iw9|2iw9]], [[1w8c|1w8c]], [[1buh|1buh]], [[2bpm|2bpm]], [[2bts|2bts]], [[1fvv|1fvv]], [[1okw|1okw]], [[2a4l|2a4l]], [[2vtp|2vtp]], [[2c6t|2c6t]], [[1fvt|1fvt]], [[1qmz|1qmz]], [[2vu3|2vu3]], [[2b55|2b55]], [[1ogu|1ogu]], [[1pf8|1pf8]], [[1h1s|1h1s]], [[2jgz|2jgz]], [[2c5v|2c5v]], [[2bhe|2bhe]], [[1urw|1urw]], [[1oiy|1oiy]], [[2c6l|2c6l]], [[1f5q|1f5q]], [[2c6o|2c6o]], [[2vtl|2vtl]], [[1ol1|1ol1]], [[1h01|1h01]], [[2uzb|2uzb]], [[1oir|1oir]], [[1oi9|1oi9]], [[2vtj|2vtj]], [[2cjm|2cjm]], [[2c5n|2c5n]], [[2c5x|2c5x]], [[2c6m|2c6m]], [[1oit|1oit]], [[2v22|2v22]], [[1gy3|1gy3]], [[1gii|1gii]], [[1di8|1di8]], [[2vv9|2vv9]], [[1e9h|1e9h]], [[2vto|2vto]], [[1dm2|1dm2]], [[2uzo|2uzo]], [[1h24|1h24]], [[1h00|1h00]], [[2exm|2exm]], [[2clx|2clx]], [[1pxp|1pxp]], [[2cch|2cch]], [[2btr|2btr]], [[1b39|1b39]], [[1aq1|1aq1]], [[1h0w|1h0w]], [[1g5s|1g5s]], [[1ckp|1ckp]], [[1ke8|1ke8]], [[1pxl|1pxl]], [[1h28|1h28]], [[1h26|1h26]], [[2vtr|2vtr]], [[1e1x|1e1x]], [[1h07|1h07]], [[1y8y|1y8y]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L0F:N-[3-(1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL]BENZAMIDE'>L0F</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></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=2w1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w1h OCA], [https://pdbe.org/2w1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w1h RCSB], [https://www.ebi.ac.uk/pdbsum/2w1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w1h ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2w1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w1h OCA], [http://pdbe.org/2w1h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2w1h RCSB], [http://www.ebi.ac.uk/pdbsum/2w1h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2w1h ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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>
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Berdini V]]
[[Category: Berdini, V]]
[[Category: Boulstridge JA]]
[[Category: Boulstridge, J A]]
[[Category: Carr MG]]
[[Category: Brien, M A.O]]
[[Category: Cross DM]]
[[Category: Carr, M G]]
[[Category: Curry J]]
[[Category: Cross, D M]]
[[Category: Devine LA]]
[[Category: Curry, J]]
[[Category: Early TR]]
[[Category: Devine, L A]]
[[Category: Fazal L]]
[[Category: Early, T R]]
[[Category: Gill AL]]
[[Category: Fazal, L]]
[[Category: Heathcote M]]
[[Category: Gill, A L]]
[[Category: Howard S]]
[[Category: Heathcote, M]]
[[Category: Maman S]]
[[Category: Howard, S]]
[[Category: Matthews JE]]
[[Category: Maman, S]]
[[Category: McMenamin RL]]
[[Category: Matthews, J E]]
[[Category: Navarro EF]]
[[Category: McMenamin, R L]]
[[Category: O'Brien MA]]
[[Category: Navarro, E F]]
[[Category: O'Reilly M]]
[[Category: Rees, D C]]
[[Category: Rees DC]]
[[Category: Reilly, M O]]
[[Category: Reule M]]
[[Category: Reule, M]]
[[Category: Tisi D]]
[[Category: Tisi, D]]
[[Category: Vinkovic M]]
[[Category: Vinkovic, M]]
[[Category: Williams G]]
[[Category: Williams, G]]
[[Category: Wyatt PG]]
[[Category: Wyatt, P G]]
[[Category: Atp-binding]]
[[Category: Cell cycle]]
[[Category: Cell division]]
[[Category: Fragment screening]]
[[Category: Kinase]]
[[Category: Mitosis]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Polymorphism]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Structure based drug design]]

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