4P9V

Grb2 SH2 complexed with a pTyr-Ac6cN-Asn tripeptide

4P9V の概要

• エントリーDOI: 10.2210/pdb4p9v/pdb
• 関連するPDBエントリー: 3S8O 4P9Z
• 分子名称: Growth factor receptor-bound protein 2, PHQ-PTR-02K-ASN-NH2, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: grb2 sh2, cation-pi interaction, signaling protein-antagonist complex, signaling protein/antagonist
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14445.02

構造登録者

Clements, J.H.,Martin, S.F. (登録日: 2014-04-06, 公開日: 2014-06-18, 最終更新日: 2024-11-13)

主引用文献

Myslinski, J.M.,Clements, J.H.,Martin, S.F.
Protein-ligand interactions: Probing the energetics of a putative cation-pi interaction.
Bioorg.Med.Chem.Lett., 24:3164-3167, 2014

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.

PubMed: 24856058
DOI: 10.1016/j.bmcl.2014.04.114

実験手法

X-RAY DIFFRACTION (1.64 Å)