1f5q: Difference between revisions

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-[[Image:1f5q.gif|left|200px]]
- {{Structure
+==CRYSTAL STRUCTURE OF MURINE GAMMA HERPESVIRUS CYCLIN COMPLEXED TO HUMAN CYCLIN DEPENDENT KINASE 2==
-|PDB= 1f5q |SIZE=350|CAPTION= <scene name='initialview01'>1f5q</scene>, resolution 2.50&Aring;
+<StructureSection load='1f5q' size='340' side='right'caption='[[1f5q]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene>
+<table><tr><td colspan='2'>[[1f5q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Murid_gammaherpesvirus_4 Murid gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F5Q FirstGlance]. <br>
-|ACTIVITY=
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-|GENE=
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=1f5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f5q OCA], [https://pdbe.org/1f5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f5q RCSB], [https://www.ebi.ac.uk/pdbsum/1f5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f5q 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/f5/1f5q_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=1f5q ConSurf].
+<div style="clear:both"></div>
-'''CRYSTAL STRUCTURE OF MURINE GAMMA HERPESVIRUS CYCLIN COMPLEXED TO HUMAN CYCLIN DEPENDENT KINASE 2'''
+==See Also==
+*[[Cyclin 3D structures|Cyclin 3D structures]]
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
-==Overview==
+== References ==
-Several gamma-herpesviruses encode proteins related to the mammalian cyclins, regulatory subunits of cyclin-dependent kinases (cdks) essential for cell cycle progression. We report a 2.5 A crystal structure of a full-length oncogenic viral cyclin from gamma-herpesvirus 68 complexed with cdk2. The viral cyclin binds cdk2 with an orientation different from cyclin A and makes several novel interactions at the interface, yet it activates cdk2 by triggering conformational changes similar to cyclin A. Sequences within the viral cyclin N-terminus lock part of the cdk2 T-loop within the core of the complex. These sequences and others are conserved amongst the viral and cellular D-type cyclins, suggesting that this structure has wider implications for other cyclin-cdk complexes. The observed resistance of this viral cyclin-cdk complex to inhibition by the p27(KIP:) cdk inhibitor is explained by sequence and conformational variation in the cyclin rendering the p27(KIP:)-binding site on the cyclin subunit non-functional.
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-F5Q is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Murid_herpesvirus_1 Murid herpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F5Q OCA].
-==Reference==
-Crystal structure of a gamma-herpesvirus cyclin-cdk complex., Card GL, Knowles P, Laman H, Jones N, McDonald NQ, EMBO J. 2000 Jun 15;19(12):2877-88. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10856233 10856233]
 [[Category: Homo sapiens]]
-[[Category: Murid herpesvirus 1]]
+[[Category: Large Structures]]
-[[Category: Protein complex]]
+[[Category: Murid gammaherpesvirus 4]]
-[[Category: Card, G L.]]
+[[Category: Card GL]]
-[[Category: Jones, N.]]
+[[Category: Jones N]]
-[[Category: Knowles, P.]]
+[[Category: Knowles P]]
-[[Category: Laman, H.]]
+[[Category: Laman H]]
-[[Category: McDonald, N Q.]]
+[[Category: McDonald NQ]]
-[[Category: CL]]
-[[Category: cyclin dependent kinase. protein/protein complex]]
-[[Category: herpesviral cyclin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:04:50 2008''