4cfm: Difference between revisions

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 ==Structure-based design of C8-substituted O6-cyclohexylmethoxyguanine CDK1 and 2 inhibitors.==
-<StructureSection load='4cfm' size='340' side='right' caption='[[4cfm]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
+<StructureSection load='4cfm' size='340' side='right'caption='[[4cfm]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4cfm]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CFM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CFM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4cfm]] is a 4 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=4CFM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CFM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4QE:6-(CYCLOHEXYLMETHOXY)-8-(2-METHYLPHENYL)-9H-PURIN-2-AMINE'>4QE</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]] 2.85&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4QE:6-(CYCLOHEXYLMETHOXY)-8-(2-METHYLPHENYL)-9H-PURIN-2-AMINE'>4QE</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-<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=4cfm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cfm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cfm RCSB], [http://www.ebi.ac.uk/pdbsum/4cfm PDBsum]</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=4cfm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cfm OCA], [https://pdbe.org/4cfm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cfm RCSB], [https://www.ebi.ac.uk/pdbsum/4cfm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cfm 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4cfm" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cyclin 3D structures|Cyclin 3D structures]]
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Anscombe, E]]
+[[Category: Homo sapiens]]
-[[Category: Campbell, A]]
+[[Category: Large Structures]]
-[[Category: Cano, C]]
+[[Category: Anscombe E]]
-[[Category: Carbain, B]]
+[[Category: Campbell A]]
-[[Category: Echalier, A]]
+[[Category: Cano C]]
-[[Category: Endicott, J]]
+[[Category: Carbain B]]
-[[Category: Golding, B T]]
+[[Category: Echalier A]]
-[[Category: Griffin, R]]
+[[Category: Endicott J]]
-[[Category: Haggerty, K]]
+[[Category: Golding BT]]
-[[Category: Hardcastle, I R]]
+[[Category: Griffin R]]
-[[Category: Jewsbury, P]]
+[[Category: Haggerty K]]
-[[Category: Newell, D R]]
+[[Category: Hardcastle IR]]
-[[Category: Noble, M E.M]]
+[[Category: Jewsbury P]]
-[[Category: Paterson, D J]]
+[[Category: Newell DR]]
-[[Category: Roche, C]]
+[[Category: Noble MEM]]
-[[Category: Wang, L Z]]
+[[Category: Paterson DJ]]
-[[Category: Cell cycle]]
+[[Category: Roche C]]
-[[Category: Conformational restraint]]
+[[Category: Wang LZ]]
-[[Category: Cyclin dependent kinase]]
-[[Category: Reversed binding mode]]
-[[Category: Structure-based drug design]]