1WYX

The Crystal Structure of the p130Cas SH3 Domain at 1.1 A Resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.14 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The 1.1 A resolution crystal structure of the p130cas SH3 domain and ramifications for ligand selectivity

Wisniewska, M.Bossenmaier, B.Georges, G.Hesse, F.Dangl, M.Kunkele, K.P.Ioannidis, I.Huber, R.Engh, R.A.

(2005) J Mol Biol 347: 1005-1014

  • DOI: https://doi.org/10.1016/j.jmb.2005.02.017
  • Primary Citation of Related Structures:  
    1WYX

  • PubMed Abstract: 

    The Crk-associated tyrosine kinase substrate p130cas (CAS) is a docking protein containing an SH3 domain near its N terminus, followed by a short proline-rich segment, a large central substrate domain composed of 15 repeats of the four amino acid sequence YxxP, a serine-rich region and a carboxy-terminal domain, which possesses consensus binding sites for the SH2 and SH3 domains of Src (YDYV and RPLPSPP, respectively). The SH3 domain of CAS mediates its interaction with several proteins involved in signaling pathways such as focal adhesion kinase (FAK), tyrosine phosphatases PTP1B and PTP-PEST, and the guanine nucleotide exchange factor C3G. As a homolog of the corresponding Src docking domain, the CAS SH3 domain binds to proline-rich sequences (PxxP) of its interacting partners that can adopt a polyproline type II helix. We have determined a high-resolution X-ray structure of the recombinant human CAS SH3 domain. The domain, residues 1-69, crystallized in two related space groups, P2(1) and C222(1), that provided diffraction data to 1.1 A and 2.1 A, respectively. The crystal structure shows, in addition to the conserved SH3 domain architecture, the way in which the CAS characteristic amino acids form an atypically charged ligand-binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by the CAS SH3 domain. The structure enables modelling of the docking interactions to its ligands, for example from focal adhesion kinase, and supports structure-based drug design of inhibitors of the CAS-FAK interaction.


  • Organizational Affiliation

    Max Planck Institut für Biochemie, Strukturforschung, D-82152 Martinsried, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CRK-associated substrate
A, B
69Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P56945 (Homo sapiens)
Explore P56945 
Go to UniProtKB:  P56945
PHAROS:  P56945
GTEx:  ENSG00000050820 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56945
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
D [auth B]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.14 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.071α = 90
b = 56.193β = 116.22
c = 37.924γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
CCP4data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-04-26
    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: 2024-03-13
    Changes: Data collection, Database references, Derived calculations