4AXA

Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

At13148 is a Novel, Oral Multi-Agc Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity.

Yap, T.A., Walton, M.I., Grimshaw, K.M., Te Poele, R.H., Eve, P.D., Valenti, M.R., De Haven Brandon, A.K., Martins, V., Zetterlund, A., Heaton, S.P., Heinzmann, K., Jones, P.S., Feltell, R.E., Reule, M., Woodhead, S.J., Davies, T.G., Lyons, J.F., Raynaud, F.I., Eccles, S.A., Workman, P., Thompson, N.T., Garrett, M.D.

(2012) Clin Cancer Res 18: 3912

  • DOI: https://doi.org/10.1158/1078-0432.CCR-11-3313
  • Primary Citation of Related Structures:  
    4AXA

  • PubMed Abstract: 

    Deregulated phosphatidylinositol 3-kinase pathway signaling through AGC kinases including AKT, p70S6 kinase, PKA, SGK and Rho kinase is a key driver of multiple cancers. The simultaneous inhibition of multiple AGC kinases may increase antitumor activity and minimize clinical resistance compared with a single pathway component.

    • Organizational Affiliation: 

    Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT ALPHA351Bos taurusMutation(s): 4 
EC: 2.7.11.11
UniProt
Find proteins for P00517 (Bos taurus)
Explore P00517 
Go to UniProtKB:  P00517
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00517
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CAMP-DEPENDENT PROTEIN KINASE INHIBITOR ALPHAB [auth I]20Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P61925 (Homo sapiens)
Explore P61925 
Go to UniProtKB:  P61925
PHAROS:  P61925
GTEx:  ENSG00000171033 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61925
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
RKD
Query on RKD
Download Ideal Coordinates CCD File 
C [auth A](2S)-2-(4-chlorophenyl)-2-hydroxy-2-[4-(1H-pyrazol-4-yl)phenyl]ethanaminium
C17 H17 Cl N3 O
IIRWNGPLJQXWFJ-KRWDZBQOSA-O
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
RKD PDBBind:  4AXA IC50: 10 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.914α = 90
b = 74.664β = 90
c = 80.184γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-25
    Type: Initial release
  • Version 1.1: 2013-02-06
    Changes: Atomic model