4nst

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{{STRUCTURE_4nst| PDB=4nst | SCENE= }}
 
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===Crystal structure of human Cdk12/Cyclin K in complex with ADP-aluminum fluoride===
 
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==Disease==
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==Crystal structure of human Cdk12/Cyclin K in complex with ADP-aluminum fluoride==
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[[http://www.uniprot.org/uniprot/CDK12_HUMAN CDK12_HUMAN]] Chromosomal aberrations involving CDK12 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with ERBB2, leading to CDK12-ERBB2 fusion leading to trunctated CDK12 protein not in-frame with ERBB2.
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<StructureSection load='4nst' size='340' side='right'caption='[[4nst]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4nst]] 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=4NST OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NST FirstGlance]. <br>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nst OCA], [https://pdbe.org/4nst PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nst RCSB], [https://www.ebi.ac.uk/pdbsum/4nst PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nst ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CDK12_HUMAN CDK12_HUMAN] Chromosomal aberrations involving CDK12 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with ERBB2, leading to CDK12-ERBB2 fusion leading to trunctated CDK12 protein not in-frame with ERBB2.
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== Function ==
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[https://www.uniprot.org/uniprot/CDK12_HUMAN CDK12_HUMAN] Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogn inhibitors.<ref>PMID:11683387</ref> <ref>PMID:19651820</ref> <ref>PMID:20952539</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine the crystal structure of Cdk12/CycK and analyse its requirements for substrate recognition. Active Cdk12/CycK is arranged in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains a C-terminal extension that folds onto the N- and C-terminal lobes thereby contacting the ATP ribose. The interaction is mediated by an HE motif followed by a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed the highest activity on a CTD substrate prephosphorylated at position Ser7, whereas the common Lys7 substitution was not recognized. Flavopiridol is most potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase. These results suggest the regulation of Pol II elongation by a relay of transcriptionally active CTD kinases.
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==Function==
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The structure and substrate specificity of human Cdk12/Cyclin K.,Bosken CA, Farnung L, Hintermair C, Merzel Schachter M, Vogel-Bachmayr K, Blazek D, Anand K, Fisher RP, Eick D, Geyer M Nat Commun. 2014 Mar 24;5:3505. doi: 10.1038/ncomms4505. PMID:24662513<ref>PMID:24662513</ref>
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[[http://www.uniprot.org/uniprot/CDK12_HUMAN CDK12_HUMAN]] Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogn inhibitors.<ref>PMID:11683387</ref> <ref>PMID:19651820</ref> <ref>PMID:20952539</ref> [[http://www.uniprot.org/uniprot/CCNK_HUMAN CCNK_HUMAN]] May play a role in transcriptional regulation. In vitro, is associated with a kinase activity toward both RNA polymerase II C-terminal domain and CDK2 (CAK).<ref>PMID:10574912</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4nst]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NST OCA].
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</div>
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<div class="pdbe-citations 4nst" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Cyclin 3D structures|Cyclin 3D structures]]
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[[Category: Anand, K.]]
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*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
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[[Category: Boesken, C A.]]
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== References ==
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[[Category: Farnung, L.]]
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<references/>
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[[Category: Geyer, M.]]
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__TOC__
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[[Category: Phosphorylation]]
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</StructureSection>
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[[Category: Rna polymerase ii]]
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[[Category: Homo sapiens]]
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[[Category: Transcription]]
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[[Category: Large Structures]]
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[[Category: Transferase-transcription complex]]
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[[Category: Anand K]]
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[[Category: Boesken CA]]
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[[Category: Farnung L]]
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[[Category: Geyer M]]

Current revision

Crystal structure of human Cdk12/Cyclin K in complex with ADP-aluminum fluoride

PDB ID 4nst

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