1wcc: Difference between revisions

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-{{Seed}}
-[[Image:1wcc.png|left|200px]]
-<!--
+==screening for fragment binding by X-ray crystallography==
-The line below this paragraph, containing "STRUCTURE_1wcc", creates the "Structure Box" on the page.
+<StructureSection load='1wcc' size='340' side='right'caption='[[1wcc]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1wcc]] 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=1WCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WCC FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIG:2-AMINO-6-CHLOROPYRAZINE'>CIG</scene></td></tr>
-{{STRUCTURE_1wcc|  PDB=1wcc  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wcc OCA], [https://pdbe.org/1wcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wcc RCSB], [https://www.ebi.ac.uk/pdbsum/1wcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wcc 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/wc/1wcc_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=1wcc ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (&gt;100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper.
-===SCREENING FOR FRAGMENT BINDING BY X-RAY CRYSTALLOGRAPHY===
+Fragment-based lead discovery using X-ray crystallography.,Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854<ref>PMID:15658854</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1wcc" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15658854}}, adds the Publication Abstract to the page
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 15658854 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15658854}}
+__TOC__
+</StructureSection>
-==About this Structure==
-WCC is a [[Single protein]] 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=1WCC OCA].
-==Reference==
-Fragment-based lead discovery using X-ray crystallography., Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H, J Med Chem. 2005 Jan 27;48(2):403-13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15658854 15658854]
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Cleasby A]]
-[[Category: Cleasby, A.]]
+[[Category: Frederickson M]]
-[[Category: Frederickson, M.]]
+[[Category: Hartshorn MJ]]
-[[Category: Hartshorn, M.]]
+[[Category: Jhoti H]]
-[[Category: Jhoti, H.]]
+[[Category: Murray CW]]
-[[Category: Murray, C.]]
+[[Category: O'Reilly M]]
-[[Category: Reilly, M O.]]
+[[Category: Tickle IJ]]
-[[Category: Tickle, I.]]
-[[Category: Cdk2]]
-[[Category: Cell cycle]]
-[[Category: Fragment screening]]
-[[Category: Kinase]]
-[[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:57:06 2008''