1YHV

Crystal Structure of PAK1 kinase domain with two point mutations (K299R, T423E)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The Active Conformation of the PAK1 Kinase Domain

Lei, M.Robinson, M.A.Harrison, S.C.

(2005) Structure 13: 769-778

  • DOI: https://doi.org/10.1016/j.str.2005.03.007
  • Primary Citation of Related Structures:  
    1YHV, 1YHW

  • PubMed Abstract: 

    The p21-activated kinases (PAKs) participate in cytoskeletal control networks, downstream of Rho-family GTPases. A structure of PAK1 in an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces the latter into an inactive conformation, prevents phosphorylation of Thr423 in the activation loop, and promotes dimerization. We have now determined structures at 1.8 A resolution for the free PAK1 kinase domain, with a mutation in the active site that blocks enzymatic activity, and for the same domain with a "phosphomimetic" mutation in the activation loop. The two very similar structures show that even in the absence of a phosphorylated Thr423, the kinase has an essentially active conformation. When Cdc42 binds the regulatory region and dissociates the dimer, PAK1 will be in an "intermediate-active" state, with a capacity to phosphorylate itself or other substrates even prior to modification of its activation loop.


  • Organizational Affiliation

    Laboratory of Molecular Medicine, Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase PAK 1297Homo sapiensMutation(s): 2 
Gene Names: PAK1
EC: 2.7.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for Q13153 (Homo sapiens)
Explore Q13153 
Go to UniProtKB:  Q13153
PHAROS:  Q13153
GTEx:  ENSG00000149269 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13153
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.962α = 90
b = 103.296β = 90
c = 122.876γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-05-24
    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: 2021-10-20
    Changes: Database references
  • Version 1.4: 2024-02-14
    Changes: Data collection