4P9V: Grb2 Sh2 Complexed With A Ptyr-ac6cn-asn Tripeptide

In order to probe the energetics associated with a putative cation-pi 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, DeltaG degrees , 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-pi interactions, but there is no net energetic benefit to such an interaction in this biological system. Accordingly, although cation-pi 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.
PDB ID: 4P9VDownload
MMDB ID: 120838
PDB Deposition Date: 2014/4/6
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 1.64  Å
Source Organism:
Similar Structures:
Biological Unit for 4P9V: dimeric; determined by author and by software (PISA)
Molecular Components in 4P9V
Label Count Molecule
Protein (1 molecule)
Growth Factor Receptor-bound Protein 2(Gene symbol: GRB2)
Molecule annotation
Nucleotide(1 molecule)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB