2vu3: Difference between revisions

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-'''Unreleased structure'''
-The entry 2vu3 is ON HOLD  until Paper Publication
+==Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H- pyrazole-3-carboxamide (AT7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design.==
+<StructureSection load='2vu3' size='340' side='right'caption='[[2vu3]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2vu3]] 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=2VU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VU3 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LZE:4-{[(2,6-DICHLOROPHENYL)CARBONYL]AMINO}-N-PIPERIDIN-4-YL-1H-PYRAZOLE-3-CARBOXAMIDE'>LZE</scene></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=2vu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vu3 OCA], [https://pdbe.org/2vu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vu3 RCSB], [https://www.ebi.ac.uk/pdbsum/2vu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vu3 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/vu/2vu3_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=2vu3 ConSurf].
+<div style="clear:both"></div>
-Authors: Wyatt, P.G., Woodhead, A.J., Boulstridge, J.A., Berdini, V., Carr, M.G., Cross, D.M., Danillon, D., Davis, D.J., Devine, L.A., Early, T.R., Feltell, R.E., Lewis, J., McMenamin, R., Navarro, E.F., O'Brien, M.A., O'Reilly, M., Reule, M., Saxty, G., Seavers, L.C.A., Smith, D.M., Squires, M.S., Trewartha, G., Walker, M.T., Woolford, A.J.
+==See Also==
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
-Description: Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design.
+== References ==
+<references/>
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 23 12:09:53 2008''
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Berdini V]]
+[[Category: Boulstridge JA]]
+[[Category: Carr MG]]
+[[Category: Cross DM]]
+[[Category: Danillon D]]
+[[Category: Davis DJ]]
+[[Category: Devine LA]]
+[[Category: Early TR]]
+[[Category: Feltell RE]]
+[[Category: Lewis EJ]]
+[[Category: McMenamin RL]]
+[[Category: Navarro EF]]
+[[Category: O'Brien MA]]
+[[Category: O'Reilly M]]
+[[Category: Reule M]]
+[[Category: Saxty G]]
+[[Category: Seavers LCA]]
+[[Category: Smith D]]
+[[Category: Squires MS]]
+[[Category: Trewartha G]]
+[[Category: Walker MT]]
+[[Category: Woodhead AJ]]
+[[Category: Woolford AJ]]
+[[Category: Wyatt PG]]