3OVE: Crystal Structure Of The Grb2 Sh2 Domain In Complex With A Pyxn- Derived Tripeptide

Citation:
Abstract
Thermodynamic parameters were determined for complex formation between the Grb2 SH2 domain and Ac-pTyr-Xaa-Asn derived tripeptides in which the Xaa residue is an alpha,alpha-cycloaliphatic amino acid that varies in ring size from three- to seven-membered. Although the six- and seven-membered ring analogs are approximately equipotent, binding affinities of those having three- to six-membered rings increase incrementally with ring size because increasingly more favorable binding enthalpies dominate increasingly less favorable binding entropies, a finding consistent with an enthalpy-driven hydrophobic effect. Crystallographic analysis reveals that the only significant differences in structures of the complexes are in the number of van der Waals contacts between the domain and the methylene groups in the Xaa residues. There is a positive correlation between buried nonpolar surface area and binding free energy and enthalpy, but not with DeltaC(p). Displacing a water molecule from a protein-ligand interface is not necessarily reflected in a favorable change in binding entropy. These findings highlight some of the fallibilities associated with commonly held views of relationships of structure and energetics in protein-ligand interactions and have significant implications for ligand design.
PDB ID: 3OVEDownload
MMDB ID: 94751
PDB Deposition Date: 2010/9/16
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 1.82  Å
Source Organism:
Similar Structures:
Biological Unit for 3OVE: dimeric; determined by author and by software (PISA)
Molecular Components in 3OVE
Label Count Molecule
Protein (1 molecule)
1
Growth Factor Receptor-bound Protein 2(Gene symbol: GRB2)
Molecule annotation
Nucleotide(1 molecule)
1
Pyac7cn
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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