4NST

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

The structure and substrate specificity of human Cdk12/Cyclin K.

Bosken, C.A.Farnung, L.Hintermair, C.Merzel Schachter, M.Vogel-Bachmayr, K.Blazek, D.Anand, K.Fisher, R.P.Eick, D.Geyer, M.

(2014) Nat Commun 5: 3505-3505

  • DOI: https://doi.org/10.1038/ncomms4505
  • Primary Citation of Related Structures:  
    4NST

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    1] Group Physical Biochemistry, Center of Advanced European Studies and Research, Ludwig-Erhard-Allee 2, Bonn 53175, Germany [2] Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund 44227, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-dependent kinase 12
A, C
351Homo sapiensMutation(s): 0 
Gene Names: CDK12CRK7CRKRSKIAA0904
EC: 2.7.11.22 (PDB Primary Data), 2.7.11.23 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NYV4 (Homo sapiens)
Explore Q9NYV4 
Go to UniProtKB:  Q9NYV4
PHAROS:  Q9NYV4
GTEx:  ENSG00000167258 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NYV4
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-K
B, D
268Homo sapiensMutation(s): 0 
Gene Names: CCNKCPR4
UniProt & NIH Common Fund Data Resources
Find proteins for O75909 (Homo sapiens)
Explore O75909 
Go to UniProtKB:  O75909
PHAROS:  O75909
GTEx:  ENSG00000090061 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75909
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download Ideal Coordinates CCD File 
E [auth A],
L [auth C]
ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
AF3
Query on AF3

Download Ideal Coordinates CCD File 
F [auth A],
M [auth C]
ALUMINUM FLUORIDE
Al F3
KLZUFWVZNOTSEM-UHFFFAOYSA-K
EDO
Query on EDO

Download Ideal Coordinates CCD File 
J [auth A],
K [auth B],
P [auth C],
S [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
I [auth A]
N [auth C]
O [auth C]
G [auth A],
H [auth A],
I [auth A],
N [auth C],
O [auth C],
Q [auth D],
R [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPO
Query on TPO
A, C
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.198 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.72α = 104.04
b = 78.85β = 85.76
c = 91.49γ = 101.46
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-26
    Type: Initial release
  • Version 1.1: 2014-10-01
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description