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(-) Description

Title :  CRYSTAL STRUCTURE OF HUMAN CDK8/CYCC IN COMPLEX WITH COMPOUND 1 (N-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-4-[2-({[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]CARBAMOYL}AMINO)ETHYL]PIPERAZINE-1-CARBOXAMIDE)
 
Authors :  E. V. Schneider, J. Boettcher, R. Huber, K. Maskos
Date :  15 May 12  (Deposition) - 01 May 13  (Release) - 01 Apr 15  (Revision)
Method :  X-RAY DIFFRACTION
Resolution :  2.39
Chains :  Asym./Biol. Unit :  A,B
Keywords :  Protein Kinase Complex, Proteros, Transferase-Transcription-Inhibitor Complex (Keyword Search: [Gene Ontology, PubMed, Web (Google)] )
 
Reference :  E. V. Schneider, J. Bottcher, R. Huber, K. Maskos, L. Neumann
Structure-Kinetic Relationship Study Of Cdk8/Cycc Specific Compounds.
Proc. Natl. Acad. Sci. Usa V. 110 8081 2013
PubMed-ID: 23630251  |  Reference-DOI: 10.1073/PNAS.1305378110

(-) 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
    Expression System Vector Type: BACULOVIRUS
    Fragment: UNP RESIDUES 1-403
    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
    Expression System Vector Type: BACULOVIRUS
    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  (4, 16)

Asymmetric/Biological Unit (4, 16)
No.NameCountTypeFull Name
10SS1Ligand/IonN-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-4-[2-({[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]CARBAMOYL}AMINO)ETHYL]PIPERAZINE-1-CARBOXAMIDE
2DMS1Ligand/IonDIMETHYL SULFOXIDE
3EDO9Ligand/Ion1,2-ETHANEDIOL
4FMT5Ligand/IonFORMIC ACID

(-) Sites  (16, 16)

Asymmetric Unit (16, 16)
No.NameEvidenceResiduesDescription
01AC1SOFTWAREVAL A:27 , TYR A:32 , SER A:62 , GLU A:66 , ILE A:79 , PHE A:97 , TRP A:105 , HIS A:149 , ALA A:172 , ASP A:173 , MET A:174 , ARG A:356 , HOH A:603 , HOH A:614 , HOH A:633 , HOH A:649BINDING SITE FOR RESIDUE 0SS A 501
02AC2SOFTWARELYS A:153 , HOH A:608BINDING SITE FOR RESIDUE DMS A 502
03AC3SOFTWARESER A:343BINDING SITE FOR RESIDUE EDO A 503
04AC4SOFTWARELYS A:307BINDING SITE FOR RESIDUE EDO A 504
05AC5SOFTWAREPRO A:124 , GLY A:126 , MET A:127BINDING SITE FOR RESIDUE EDO A 505
06AC6SOFTWAREARG A:13 , GLU A:14 , VAL A:84 , PHE A:85BINDING SITE FOR RESIDUE EDO A 506
07AC7SOFTWAREVAL A:84 , ASP B:147BINDING SITE FOR RESIDUE FMT A 507
08AC8SOFTWAREGLU A:21 , TYR A:22 , GLU A:23BINDING SITE FOR RESIDUE FMT A 508
09AC9SOFTWAREALA B:0 , ALA B:2 , VAL B:152 , TYR B:153BINDING SITE FOR RESIDUE EDO B 301
10BC1SOFTWAREGLN B:49 , GLU B:53 , LEU B:57 , GLN B:59BINDING SITE FOR RESIDUE EDO B 302
11BC2SOFTWAREGLN B:161 , TYR B:162BINDING SITE FOR RESIDUE EDO B 303
12BC3SOFTWARELEU A:9 , TYR B:76 , TYR B:141 , GLU B:144 , LEU B:145BINDING SITE FOR RESIDUE EDO B 304
13BC4SOFTWARETHR A:57 , ILE A:59 , PHE B:92 , LYS B:96 , HOH B:422 , HOH B:438BINDING SITE FOR RESIDUE EDO B 305
14BC5SOFTWAREASN B:46 , ARG B:185 , GLU B:246BINDING SITE FOR RESIDUE FMT B 306
15BC6SOFTWAREGLN B:41 , THR B:45 , THR B:66 , PHE B:69 , LYS B:70 , TYR B:184BINDING SITE FOR RESIDUE FMT B 307
16BC7SOFTWARETHR B:118 , ARG B:119 , PHE B:120 , SER B:121 , ARG B:247BINDING SITE FOR RESIDUE FMT B 308

(-) SS Bonds  (0, 0)

(no "SS Bond" information available for 4F6W)

(-) 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 4F6W)

(-) PROSITE Motifs  (0, 0)

(no "PROSITE Motif" information available for 4F6W)

(-) Exons   (0, 0)

(no "Exon" information available for 4F6W)

(-) 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:330
                                                                                                                                                                                                                                                                                                                                                                          
               SCOP domains ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ SCOP domains
               CATH domains ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ CATH domains
               Pfam domains ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Pfam domains
         Sec.struct. author .hhhhhhhhhhhh.hhhhhee....eeeee..eeeeeeee........eeeeee.....hhhhhhhhhhhh.........eeeeeee....eeeeeee...eehhhhhhhhhhh....hhhhhhhhhhhhhhhhhhhhhh.......hhh.eee.........eee...........hhhhhh.....hhhhhhhhhhhhhhhhhhh...........hhhhhhhhhhhhh......hhhhhhh.hhhhhhhhhhhhhhh..hhhhhhhhh.....hhhhhhhhhhh..hhhhh.hhhhhhhhhhhhh...................... Sec.struct. author
                 SAPs(SNPs) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ SAPs(SNPs)
                    PROSITE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ PROSITE
                 Transcript ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Transcript
                 4f6w A   1 MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFATFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFL 359
                                    10        20        30        40        50        60        70        80        90       100       110    || 125       135       145       155       165       175 ||    203       213       223       233    || 249       259       269       279       289       299       309       319       329       339       349       359
                                                                                                                                            115|                                                     177|                                       238|                                                                                                                  
                                                                                                                                             121                                                      196                                        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.hhhhhhhhhhhhhh..hhhhhhhhhhhhhhhhhhhhhhhh.hhhhhhhhhhhhhhhhhhh.....hhhhhhhhhhhhhhhhh.....hhhhhhhhhhhhhhhhh..........hhhhhhhhhhhhhhhh........hhhhhhhhhhhhhhhhhhhhhhhhhhhhhh..hhhhhhhhhhhhhhhhhhhhhhh...hhhhhhh...hhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh....... Sec.struct. author
                 SAPs(SNPs) --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                    PROSITE --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- PROSITE
                 Transcript --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Transcript
                 4f6w 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 4F6W)

(-) CATH Domains  (0, 0)

(no "CATH Domain" information available for 4F6W)

(-) Pfam Domains  (0, 0)

(no "Pfam Domain" information available for 4F6W)

(-) 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 4f70 4f7j 4f7l 4f7n 4f7s 4g6l 5bnj 5cei 5fgk 5hbe 5hbh 5hbj 5hnb 5hvy 5i5z 5icp 5idn 5idp
        CDK8_HUMAN | P49336: 3rgf 4crl 4f6s 4f6u 4f70 4f7j 4f7l 4f7n 4f7s 4g6l 5bnj 5cei 5fgk 5hbe 5hbh 5hbj 5hnb 5hvy 5i5z 5icp 5idn 5idp

(-) Related Entries Specified in the PDB File

4f6s 4f6u 4f70 4f7j 4f7l 4f7n