IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. J. Mol. Biol. (0022-2836) 2011 imex curation Schneider E.V., Böttcher J., Blaesse M., Neumann L., Huber R., Maskos K. schneider@proteros.com, lneumann@proteros.com,huber@biochem.mpg.de,maskos@proteros.com 02-Aug-2013: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro fret fluorescent resonance energy transfer FRET RET FRET analysis FRET RET FRET analysis fret tag fluorescence tag visualisation by fluorescence tag fluorescence Schneider E.V., Böttcher J., Blaesse M., Neumann L., Huber R., Maskos K. schneider@proteros.com, lneumann@proteros.com,huber@biochem.mpg.de,maskos@proteros.com Accepted 2013-JUL-01 by ORCHARD 02-Aug-2013: Contacted by IntAct-Help. J. Mol. Biol. (0022-2836) 2011 Only protein-protein interactions imex curation The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. J. Mol. Biol. (0022-2836) 2011 imex curation Schneider E.V., Böttcher J., Blaesse M., Neumann L., Huber R., Maskos K. schneider@proteros.com, lneumann@proteros.com,huber@biochem.mpg.de,maskos@proteros.com 02-Aug-2013: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Schneider E.V., Böttcher J., Blaesse M., Neumann L., Huber R., Maskos K. schneider@proteros.com, lneumann@proteros.com,huber@biochem.mpg.de,maskos@proteros.com Accepted 2013-JUL-01 by ORCHARD 02-Aug-2013: Contacted by IntAct-Help. J. Mol. Biol. (0022-2836) 2011 Only protein-protein interactions imex curation sorafenib small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) ccnc_human Cyclin-C CCNC SRB11 homolog protein protein human Homo sapiens Human MAGNFWQSSHYLQWILDKQDLLKERQKDLKFLSEEEYWKLQIFFTNVIQALGEHLKLRQQVIATATVYFKRFYARYSLKSIDPVLMAPTCVFLASKVEEFGVVSNTRLIAAATSVLKTRFSYAFPKEFPYRMNHILECEFYLLELMDCCLIVYHPYRPLLQYVQDMGQEDMLLPLAWRIVNDTYRTDLCLLYPPFMIALACLHVACVVQQKDARQWFAELSVDMEKILEIIRVILKLYEQWKNFDERKEMATILSKMPKPKPPPNSEGEQGPNGSQNSSYSQS DIP protein P24863 original sequence version: 150 DIP protein P24863 original sequence version: 141 DIP protein P24863 original sequence version: 97 DIP protein P24863-1 original sequence version: 159 DIP protein P24863 original sequence version: 147 CF8AC5E94E621F4C cdk8_human Cyclin-dependent kinase 8 CDK8 Cell division protein kinase 8 Mediator of RNA polymerase II transcription subunit CDK8 Mediator complex subunit CDK8 Protein kinase K35 protein protein human Homo sapiens Human MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLTEEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTSDYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY DIP protein P49336 original sequence version: 126 DIP protein P49336 original sequence version: 115 DIP protein P49336 original sequence version: 89 DIP protein P49336-1 original sequence version: 149 DIP protein P49336 original sequence version: 138 00CBAB6CE354605F ccnc-cdk8-3 2 5 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection 4 unspecified role unspecified role neutral component neutral component spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection 3 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 1, Fig. 2b, Fig. 4, Fig. 5, Fig. 6, Fig. 8, Table 1 2.20A working 18.1%, free 22.1% The inhibitor sorafenib, an anti-cancer drug, is bound to the CDK8 hinge region within the catalytic cleft between the two kinase lobes. Both CDK8 and CCNC contain two additional amino acid residues from the purification/expression tag upstream of the methionine residue in the first position of the native sequence. ccnc-cdk8-4 1 5 unspecified role unspecified role fluorescence donor fluorescence donor region fluorescent dye fluorescent dye label fluorescent dye undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection 4 unspecified role unspecified role fluorescence accept fluorescence acceptor fluorescence accept region fluorescent dye fluorescent dye label fluorescent dye undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection direct interaction direct interaction Fig. 7 Deletion of CDK8 residues 1-22 lowers the affinity to Kd = 300.71 +/-144.59 nanomolar.