1XJD

Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Catalytic domain crystal structure of protein kinase C-theta (PKCtheta)

Xu, Z.B.Chaudhary, D.Olland, S.Wolfrom, S.Czerwinski, R.Malakian, K.Lin, L.Stahl, M.L.Joseph-McCarthy, D.Benander, C.Fitz, L.Greco, R.Somers, W.S.Mosyak, L.

(2004) J Biol Chem 279: 50401-50409

  • DOI: https://doi.org/10.1074/jbc.M409216200
  • Primary Citation of Related Structures:  
    1XJD

  • PubMed Abstract: 

    A member of the novel protein kinase C (PKC) subfamily, PKC, is an essential component of the T cell synapse and is required for optimal T cell activation and interleukin-2 production. Selective involvement of PKC in TCR signaling makes this enzyme an attractive therapeutic target in T cell-mediated disease processes. In this report we describe the crystal structure of the catalytic domain of PKC at 2.0-A resolution. Human recombinant PKC kinase domain was expressed in bacteria as catalytically active phosphorylated enzyme and co-crystallized with its subnanomolar, ATP site inhibitor staurosporine. The structure follows the classic bilobal kinase fold and shows the enzyme in its active conformation and phosphorylated state. Inhibitory interactions between conserved features of staurosporine and the ATP-binding cleft are accompanied by closing of the glycine-rich loop, which also maintains an inhibitory arrangement by blocking the phosphate recognition subsite. The two major phosphorylation sites, Thr-538 in the activation loop and Ser-695 in the hydrophobic motif, are both occupied in the structure, playing key roles in stabilizing active conformation of the enzyme and indicative of PKC autocatalytic phosphorylation and activation during bacterial expression. The PKC-staurosporine complex represents the first kinase domain crystal structure of any PKC isotypes to be determined and as such should provide valuable insight into PKC specificity and into rational drug design strategies for PKC selective leads.


  • Organizational Affiliation

    Department of Chemical and Screening Sciences, Inflammation Department, Wyeth Research, Cambridge, Massachusetts 02140, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein kinase C, theta type345Homo sapiensMutation(s): 2 
Gene Names: PKC
EC: 2.7.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q04759 (Homo sapiens)
Explore Q04759 
Go to UniProtKB:  Q04759
PHAROS:  Q04759
GTEx:  ENSG00000065675 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04759
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
STU
Query on STU

Download Ideal Coordinates CCD File 
B [auth A]STAUROSPORINE
C28 H26 N4 O3
HKSZLNNOFSGOKW-FYTWVXJKSA-N
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
TPO
Query on TPO
A
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Binding Affinity Annotations 
IDSourceBinding Affinity
STU Binding MOAD:  1XJD Ki: 0.33 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.201 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 139.566α = 90
b = 42.4β = 116.24
c = 67.678γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2004-10-19 
  • Deposition Author(s): Xu, Z.B.

Revision History  (Full details and data files)

  • Version 1.0: 2004-10-19
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description