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PDBsum entry 4g6l

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protein ligands Protein-protein interface(s) links
Transferase/transcription PDB id
4g6l
Jmol
Contents
Protein chains
336 a.a.
267 a.a.
Ligands
FMT
Waters ×40
PDB id:
4g6l
Name: Transferase/transcription
Title: Crystal structure of human cdk8/cycc in the dmg-in conformat
Structure: Cyclin-dependent kinase 8. Chain: a. Fragment: unp residues 1-403. Synonym: cell division protein kinase 8, mediator complex s cdk8, mediator of RNA polymerase ii transcription subunit c protein kinase k35. Engineered: yes. Cyclin-c. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk8. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: ccnc.
Resolution:
2.70Å     R-factor:   0.214     R-free:   0.266
Authors: E.V.Schneider,M.Blaesse,R.Huber,K.Maskos
Key ref: E.V.Schneider et al. (2013). Structure-kinetic relationship study of CDK8/CycC specific compounds. Proc Natl Acad Sci U S A, 110, 8081-8086. PubMed id: 23630251 DOI: 10.1073/pnas.1305378110
Date:
19-Jul-12     Release date:   01-May-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P49336  (CDK8_HUMAN) -  Cyclin-dependent kinase 8
Seq:
Struc:
464 a.a.
336 a.a.
Protein chain
Pfam   ArchSchema ?
P24863  (CCNC_HUMAN) -  Cyclin-C
Seq:
Struc:
283 a.a.
267 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chain A: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
   Enzyme class 2: Chain A: E.C.2.7.11.23  - [RNA-polymerase]-subunit kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate
ATP
+ [DNA-directed RNA polymerase]
= ADP
+ [DNA-directed RNA polymerase] phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   3 terms 
  Biological process     gene expression   9 terms 
  Biochemical function     protein binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.1305378110 Proc Natl Acad Sci U S A 110:8081-8086 (2013)
PubMed id: 23630251  
 
 
Structure-kinetic relationship study of CDK8/CycC specific compounds.
E.V.Schneider, J.Böttcher, R.Huber, K.Maskos, L.Neumann.
 
  ABSTRACT  
 
In contrast with the very well explored concept of structure-activity relationship, similar studies are missing for the dependency between binding kinetics and compound structure of a protein ligand complex, the structure-kinetic relationship. Here, we present a structure-kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The scaffold moiety of the compounds is anchored in the kinase deep pocket and extended with diverse functional groups toward the hinge region and the front pocket. These variations can cause the compounds to change from fast to slow binding kinetics, resulting in an improved residence time. The flip of the DFG motif ("DMG" in CDK8) to the inactive DFG-out conformation appears to have relatively little influence on the velocity of binding. Hydrogen bonding with the kinase hinge region contributes to the residence time but has less impact than hydrophobic complementarities within the kinase front pocket.