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(-) Description

Title :  CDK8-CYCC IN COMPLEX WITH [(S)-2-(4-CHLORO-PHENYL)-PYRROLIDIN-1-YL]-(3-METHYL-1H-PYRAZOLO[3,4-B]PYRIDIN-5-YL)-METHANONE
 
Authors :  D. Musil, J. Blagg, A. Mallinger, P. Czodrowski, K. Schiemann
Date :  24 Feb 16  (Deposition) - 21 Dec 16  (Release) - 21 Dec 16  (Revision)
Method :  X-RAY DIFFRACTION
Resolution :  2.26
Chains :  Asym./Biol. Unit :  A,B
Keywords :  Cdk8 Kinase / Cyclin C, Transferase (Keyword Search: [Gene Ontology, PubMed, Web (Google)] )
 
Reference :  P. Czodrowski, A. Mallinger, D. Wienke, C. Esdar, O. Poschke, M. Busch F. Rohdich, S. A. Eccles, M. J. Ortiz-Ruiz, R. Schneider, F. I. Raynaud P. A. Clarke, D. Musil, D. Schwarz, T. Dale, K. Urbahns, J. Blagg, K. Schiemann
Structure-Based Optimization Of Potent, Selective, And Orally Bioavailable Cdk8 Inhibitors Discovered By High-Throughput Screening.
J. Med. Chem. V. 59 9337 2016
PubMed-ID: 27490956  |  Reference-DOI: 10.1021/ACS.JMEDCHEM.6B00597

(-) Compounds

Molecule 1 - CYCLIN-DEPENDENT KINASE 8
    Chains: A
    EC Number: 2.7.11.22, 2.7.11.23
    Engineered: YES
    Expression System: SPODOPTERA FRUGIPERDA
    Expression System Common: FALL ARMYWORM
    Expression System Taxid: 7108
    Fragment: KINASE DOMAIN, RESIDUES 3-405
    Gene: CDK8
    Organism Common: HUMAN
    Organism Scientific: HOMO SAPIENS
    Organism Taxid: 9606
    Synonym: CELL DIVISION PROTEIN KINASE 8,MEDIATOR COMPLEX SUBUNIT CDK8,MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT CDK8,PROTEIN KINASE K35
 
Molecule 2 - CYCLIN-C
    Chains: B
    Engineered: YES
    Expression System: SPODOPTERA FRUGIPERDA
    Expression System Common: FALL ARMYWORM
    Expression System Taxid: 7108
    Gene: CCNC
    Organism Common: HUMAN
    Organism Scientific: HOMO SAPIENS
    Organism Taxid: 9606
    Synonym: SRB11 HOMOLOG,HSRB11

 Structural Features

(-) Chains, Units

  12
Asymmetric/Biological Unit : AB

Summary Information (see also Sequences/Alignments below)

(-) Ligands, Modified Residues, Ions  (3, 8)

Asymmetric/Biological Unit (3, 8)
No.NameCountTypeFull Name
16A71Ligand/Ion[(2S)-2-(4-CHLOROPHENYL)PYRROLIDIN-1-YL](3-METHYL-1H-PYRAZOLO[3,4-B]PYRIDIN-5-YL)METHANONE
2EDO1Ligand/Ion1,2-ETHANEDIOL
3FMT6Ligand/IonFORMIC ACID

(-) Sites  (8, 8)

Asymmetric Unit (8, 8)
No.NameEvidenceResiduesDescription
1AC1SOFTWAREVAL A:27 , GLY A:28 , TYR A:32 , ALA A:50 , LYS A:52 , ILE A:79 , PHE A:97 , ASP A:98 , TYR A:99 , ALA A:100 , ALA A:155 , LEU A:158 , ASP A:173 , ARG A:356binding site for residue 6A7 A 401
2AC2SOFTWAREARG A:125 , VAL A:302 , LYS A:303binding site for residue EDO A 402
3AC3SOFTWAREHIS A:149 , ASP A:151 , ASP A:173 , PHE A:176binding site for residue FMT A 403
4AC4SOFTWARETYR A:32 , LYS A:52 , SER A:62 , ALA A:63binding site for residue FMT A 404
5AC5SOFTWAREGLU A:17 , TYR A:22 , SER A:87 , ASP A:90 , TRP A:94binding site for residue FMT A 405
6AC6SOFTWAREALA B:2 , GLY B:3 , TYR B:153 , ARG B:157 , FMT B:302 , HOH B:414binding site for residue FMT B 301
7AC7SOFTWAREALA B:0 , TYR B:153 , FMT B:301 , HOH B:437binding site for residue FMT B 302
8AC8SOFTWAREHIS B:203 , LYS B:211 , ASP B:212 , ALA B:213 , ARG B:214binding site for residue FMT B 303

(-) SS Bonds  (0, 0)

(no "SS Bond" information available for 5IDN)

(-) Cis Peptide Bonds  (1, 1)

Asymmetric/Biological Unit
No.Residues
1Asp A:338 -Pro A:339

 Sequence-Structure Mapping

(-) SAPs(SNPs)/Variants  (0, 0)

(no "SAP(SNP)/Variant" information available for 5IDN)

(-) PROSITE Motifs  (0, 0)

(no "PROSITE Motif" information available for 5IDN)

(-) Exons   (0, 0)

(no "Exon" information available for 5IDN)

(-) Sequences/Alignments

Asymmetric/Biological Unit
   Reformat: Number of residues per line =  ('0' or empty: single-line sequence representation)
  Number of residues per labelling interval =   
  UniProt sequence: complete  aligned part    
   Show mapping: SCOP domains CATH domains Pfam domains Secondary structure (by author)
SAPs(SNPs) PROSITE motifs Exons
(details for a mapped element are shown in a popup box when the mouse pointer rests over it) 
Chain A from PDB  Type:PROTEIN  Length:336
                                                                                                                                                                                                                                                                                                                                                                                
               SCOP domains ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ SCOP domains
               CATH domains ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ CATH domains
               Pfam domains ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Pfam domains
         Sec.struct. author .hhhhhhhhhhhh.hhhhhee....eeeee..eeeeeeee........eeeeee.....hhhhhhhhhhhhhh.......eeeeeee....eeeeeee...eehhhhhhhhhhhh...hhhhhhhhhhhhhhhhhhhhhh.......hhh.eee.........eee.............hhhhhh.....hhhhhhhhhhhhhhhhhhh...........hhhhhhhhhhhhh......hhhhhhh.hhhhhhhhhhhhhhh..hhhhhhhhh.....hhhhhhhhhhh..hhhhh.hhhhhhhhhhhh........................... Sec.struct. author
                 SAPs(SNPs) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ SAPs(SNPs)
                    PROSITE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ PROSITE
                 Transcript ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Transcript
                 5idn A   1 MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLTEEE 363
                                    10        20        30        40        50        60        70        80        90       100       110      |125       135       145       155       165       175  ||   201       211       221       231      |247       257       267       277       287       297       307       317       327       337       347       357      
                                                                                                                                              117|                                                    178|                                        238|                                                                                                                      
                                                                                                                                               123                                                     195                                         245                                                                                                                      


Chain B from PDB  Type:PROTEIN  Length:267
                                                                                                                                                                                                                                                                                                           
               SCOP domains --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author ......hhhhhhhhhhhh.hhhhhhhhhh......hhhhhhhhhhhhhhhhhhhhhhh..hhhhhhhhhhhhhhhhhhh.....hhhhhhhhhhhhhhhhh.....hhhhhhhhhhhhhhhh...........hhhhhhhhhhhhhhhh........hhhhhhhhhhhhhhhhhhhhhhhhhhhhhh..hhhhhhhhhhhhhhhhhhhhhhh...hhhhhhh...hhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh........ Sec.struct. author
                 SAPs(SNPs) --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                    PROSITE --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- PROSITE
                 Transcript --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Transcript
                 5idn B  -2 DKAMAGNFWQSSHYLQWILDKQDLLKERQKDLKFLSEEEYWKLQIFFTNVIQALGEHLKLRQQVIATATVYFKRFYARYSLKSIDPVLMAPTCVFLASKVEEFGVVSNTRLIAAATSVLKTRFSYAFPKEFPYRMNHILECEFYLLELMDCCLIVYHPYRPLLQYVQDMGQEDMLLPLAWRIVNDTYRTDLCLLYPPFMIALACLHVACVVQQKDARQWFAELSVDMEKILEIIRVILKLYEQWKNFDERKEMATILSKMPKPKPPP 264
                                     7        17        27        37        47        57        67        77        87        97       107       117       127       137       147       157       167       177       187       197       207       217       227       237       247       257
   Legend:   → Mismatch (orange background)
  - → Gap (green background, '-', border residues have a numbering label)
    → Modified Residue (blue background, lower-case, 'x' indicates undefined single-letter code, labelled with number + name)
  x → Chemical Group (purple background, 'x', labelled with number + name, e.g. ACE or NH2)
  extra numbering lines below/above indicate numbering irregularities and modified residue names etc., number ends below/above '|'

 Classification and Annotation

(-) SCOP Domains  (0, 0)

(no "SCOP Domain" information available for 5IDN)

(-) CATH Domains  (0, 0)

(no "CATH Domain" information available for 5IDN)

(-) Pfam Domains  (0, 0)

(no "Pfam Domain" information available for 5IDN)

(-) Gene Ontology  (27, 37)

Asymmetric/Biological Unit(hide GO term definitions)

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  Cis Peptide Bonds
    Asp A:338 - Pro A:339   [ RasMol ]  
 

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  CDK8_HUMAN | P49336
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  2.7.11.22
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 Related Entries

(-) Entries Sharing at Least One Protein Chain (UniProt ID)

UniProtKB/Swiss-Prot
        CCNC_HUMAN | P24863: 3rgf 4crl 4f6s 4f6u 4f6w 4f70 4f7j 4f7l 4f7n 4f7s 4g6l 5bnj 5cei 5fgk 5hbe 5hbh 5hbj 5hnb 5hvy 5i5z 5icp 5idp
        CDK8_HUMAN | P49336: 3rgf 4crl 4f6s 4f6u 4f6w 4f70 4f7j 4f7l 4f7n 4f7s 4g6l 5bnj 5cei 5fgk 5hbe 5hbh 5hbj 5hnb 5hvy 5i5z 5icp 5idp

(-) Related Entries Specified in the PDB File

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