2F57

Crystal Structure Of The Human P21-Activated Kinase 5


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.155 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.

Eswaran, J.Lee, W.H.Debreczeni, J.E.Filippakopoulos, P.Turnbull, A.Fedorov, O.Deacon, S.W.Peterson, J.R.Knapp, S.

(2007) Structure 15: 201-213

  • DOI: https://doi.org/10.1016/j.str.2007.01.001
  • Primary Citation of Related Structures:  
    2BVA, 2C30, 2CDZ, 2F57

  • PubMed Abstract: 

    p21-activated kinases have been classified into two groups based on their domain architecture. Group II PAKs (PAK4-6) regulate a wide variety of cellular functions, and PAK deregulation has been linked to tumor development. Structural comparison of five high-resolution structures comprising all active, monophosphorylated group II catalytic domains revealed a surprising degree of domain plasticity, including a number of catalytically productive and nonproductive conformers. Rearrangements of helix alphaC, a key regulatory element of kinase function, resulted in an additional helical turn at the alphaC N terminus and a distortion of its C terminus, a movement hitherto unseen in protein kinases. The observed structural changes led to the formation of interactions between conserved residues that structurally link the glycine-rich loop, alphaC, and the activation segment and firmly anchor alphaC in an active conformation. Inhibitor screening identified six potent PAK inhibitors from which a tri-substituted purine inhibitor was cocrystallized with PAK4 and PAK5.


  • Organizational Affiliation

    University of Oxford, Structural Genomics Consortium, Botnar Research Centre, Oxford OX3 7LD, United Kingdom. jeyanthy.eswaran@sgc.ox.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase PAK 7
A, B
317Homo sapiensMutation(s): 1 
EC: 2.7.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for Q9P286 (Homo sapiens)
Explore Q9P286 
Go to UniProtKB:  Q9P286
PHAROS:  Q9P286
GTEx:  ENSG00000101349 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9P286
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
23D
Query on 23D

Download Ideal Coordinates CCD File 
E [auth B]N2-[(1R,2S)-2-AMINOCYCLOHEXYL]-N6-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE
C19 H24 Cl N7
UTBSBSOBZHXMHI-HUUCEWRRSA-N
TRS
Query on TRS

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A, B
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.155 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.661α = 90
b = 56.599β = 103.13
c = 120.764γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-12-13
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2018-01-31
    Changes: Structure summary
  • Version 1.4: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description