4P9V

Grb2 SH2 complexed with a pTyr-Ac6cN-Asn tripeptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.64 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.7 of the entry. See complete history


Literature

Protein-ligand interactions: Probing the energetics of a putative cation-pi interaction.

Myslinski, J.M.Clements, J.H.Martin, S.F.

(2014) Bioorg Med Chem Lett 24: 3164-3167

  • DOI: https://doi.org/10.1016/j.bmcl.2014.04.114
  • Primary Citation of Related Structures:  
    4P9V, 4P9Z

  • PubMed Abstract: 

    In order to probe the energetics associated with a putative cation-π interaction, thermodynamic parameters are determined for complex formation between the Grb2 SH2 domain and tripeptide derivatives of RCO-pTyr-Ac6c-Asn wherein the R group is varied to include different alkyl, cycloalkyl, and aryl groups. Although an indole ring is reputed to have the strongest interaction with a guanidinium ion, binding free energies, ΔG°, for derivatives of RCO-pTyr-Ac6c-Asn bearing cyclohexyl and phenyl groups were slightly more favorable than their indolyl analog. Crystallographic analysis of two complexes reveals that test ligands bind in similar poses with the notable exception of the relative orientation and proximity of the phenyl and indolyl rings relative to an arginine residue of the domain. These spatial orientations are consistent with those observed in other cation-π interactions, but there is no net energetic benefit to such an interaction in this biological system. Accordingly, although cation-π interactions are well documented as important noncovalent forces in molecular recognition, the energetics of such interactions may be mitigated by other nonbonded interactions and solvation effects in protein-ligand associations.


  • Organizational Affiliation

    The Department of Chemistry, The Institute of Cellular and Molecular Biology, and the Texas Institute of Drug and Diagnostic Development, The University of Texas, Austin, TX 78712, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Growth factor receptor-bound protein 2117Homo sapiensMutation(s): 0 
Gene Names: GRB2ASH
UniProt & NIH Common Fund Data Resources
Find proteins for P62993 (Homo sapiens)
Explore P62993 
Go to UniProtKB:  P62993
PHAROS:  P62993
GTEx:  ENSG00000177885 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62993
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PHQ-PTR-02K-ASN-NH25synthetic constructMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
02K
Query on 02K
B
PEPTIDE LINKINGC7 H13 N O2ALA
PTR
Query on PTR
B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.64 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.935α = 90
b = 41.935β = 90
c = 108.715γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM 84965
National Science Foundation (NSF, United States)United StatesCHE 0750329
Robert A. Welch FoundationUnited StatesF-652

Revision History  (Full details and data files)

  • Version 1.0: 2014-06-18
    Type: Initial release
  • Version 1.1: 2014-07-16
    Changes: Database references
  • Version 1.2: 2014-12-24
    Changes: Database references
  • Version 1.3: 2017-08-09
    Changes: Database references, Derived calculations, Other, Source and taxonomy
  • Version 1.4: 2017-09-27
    Changes: Author supporting evidence
  • Version 1.5: 2019-11-27
    Changes: Author supporting evidence
  • Version 1.6: 2023-09-27
    Changes: Data collection, Database references, Refinement description
  • Version 1.7: 2023-11-15
    Changes: Data collection