4CT1

Human PDK1-PKCzeta Kinase Chimera in Complex with Allosteric Compound PS315 Bound to the PIF-Pocket


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Molecular Mechanism of Regulation of the Atypical Protein Kinase C by N-Terminal Domains and an Allosteric Small Compound.

Zhang, H.Neimanis, S.Lopez-Garcia, L.A.Arencibia, J.M.Amon, S.Stroba, A.Zeuzem, S.Proschak, E.Stark, H.Bauer, A.F.Busschots, K.Jorgensen, T.J.Engel, M.Schulze, J.O.Biondi, R.M.

(2014) Chem Biol 21: 754

  • DOI: https://doi.org/10.1016/j.chembiol.2014.04.007
  • Primary Citation of Related Structures:  
    4CT1, 4CT2

  • PubMed Abstract: 

    Protein kinases play important regulatory roles in cells and organisms. Therefore, they are subject to specific and tight mechanisms of regulation that ultimately converge on the catalytic domain and allow the kinases to be activated or inhibited only upon the appropriate stimuli. AGC protein kinases have a pocket in the catalytic domain, the PDK1-interacting fragment (PIF)-pocket, which is a key mediator of the activation. We show here that helix αC within the PIF-pocket of atypical protein kinase C (aPKC) is the target of the interaction with its inhibitory N-terminal domains. We also provide structural evidence that the small compound PS315 is an allosteric inhibitor that binds to the PIF-pocket of aPKC. PS315 exploits the physiological dynamics of helix αC for its binding and allosteric inhibition. The results will support research on allosteric mechanisms and selective drug development efforts against PKC isoforms.


  • Organizational Affiliation

    Research Group PhosphoSites, Department of Internal Medicine I, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1311Homo sapiensMutation(s): 10 
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O15530 (Homo sapiens)
Explore O15530 
Go to UniProtKB:  O15530
PHAROS:  O15530
GTEx:  ENSG00000140992 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO15530
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 148.6α = 90
b = 44.61β = 101.84
c = 48γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-05-28
    Type: Initial release
  • Version 1.1: 2014-06-04
    Changes: Atomic model
  • Version 1.2: 2014-07-02
    Changes: Database references
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description