3blh: Difference between revisions

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-{{Seed}}
-[[Image:3blh.jpg|left|200px]]
-<!--
+==Crystal Structure of Human CDK9/cyclinT1==
-The line below this paragraph, containing "STRUCTURE_3blh", creates the "Structure Box" on the page.
+<StructureSection load='3blh' size='340' side='right'caption='[[3blh]], [[Resolution|resolution]] 2.48&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'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BLH 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]] 2.48&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-{{STRUCTURE_3blh|  PDB=3blh  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [https://pdbe.org/3blh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [https://www.ebi.ac.uk/pdbsum/3blh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3blh ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
+== Function ==
+[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</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/bl/3blh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3blh ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II. To understand the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2. There are distinct differences between CDK9/CycT1 and the cell cycle CDK CDK2/CycA manifested by a relative rotation of 26 degrees of CycT1 with respect to the CDK, showing for the first time plasticity in CDK cyclin interactions. The CDK9/CycT1 interface is relatively sparse but retains some core CDK-cyclin interactions. The CycT1 C-terminal helix shows flexibility that may be important for the interaction of this region with HIV TAT and HEXIM. Flavopiridol, an anticancer drug in phase II clinical trials, binds to the ATP site of CDK9 inducing unanticipated structural changes that bury the inhibitor. CDK9 activity and recognition of regulatory proteins are governed by autophosphorylation. We show that CDK9/CycT1 autophosphorylates on Thr186 in the activation segment and three C-terminal phosphorylation sites. Autophosphorylation on all sites occurs in cis.
-===Crystal Structure of Human CDK9/cyclinT1===
+The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation.,Baumli S, Lolli G, Lowe ED, Troiani S, Rusconi L, Bullock AN, Debreczeni JE, Knapp S, Johnson LN EMBO J. 2008 Jul 9;27(13):1907-18. Epub 2008 Jun 19. PMID:18566585<ref>PMID:18566585</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3blh" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18566585}}, adds the Publication Abstract to the page
+*[[Cyclin|Cyclin]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18566585 is the PubMed ID number.
+*[[Cyclin 3D structures|Cyclin 3D structures]]
--->
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
-{{ABSTRACT_PUBMED_18566585}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-BLH is a [[Protein complex]] structure of sequences 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=3BLH OCA].
+</StructureSection>
-==Reference==
-The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation., Baumli S, Lolli G, Lowe ED, Troiani S, Rusconi L, Bullock AN, Debreczeni JE, Knapp S, Johnson LN, EMBO J. 2008 Jun 19;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18566585 18566585]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Baumli, S.]]
+[[Category: Baumli S]]
-[[Category: Johnson, L N.]]
+[[Category: Johnson LN]]
-[[Category: Lolli, G.]]
+[[Category: Lolli G]]
-[[Category: Lowe, E D.]]
+[[Category: Lowe ED]]
-[[Category: Acetylation]]
-[[Category: Alternative splicing]]
-[[Category: Atp-binding]]
-[[Category: Cell cycle]]
-[[Category: Cell division]]
-[[Category: Coiled coil]]
-[[Category: Host-virus interaction]]
-[[Category: Kinase]]
-[[Category: Nucleotide-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Phosphorylated]]
-[[Category: Polymorphism]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transcription regulation]]
-[[Category: Transcriptional cdk/cyclin complex]]
-[[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul  3 11:25:48 2008''