C-H times times times O Hydrogen Bonds in the Nuclear Receptor RAR gamma --a Potential Tool for Drug Selectivity

• Published in: Structure (London) Vol. 10; no. 9; pp. 1197 - 1204
• Main Authors: Klaholz, B P, Moras, D
• Format: Journal Article
• Language: English
• Published: 01.09.2002
• ISSN: 0969-2126
• DOI: 10.1016/S0969-2126(02)00828-6

Hydrogen bonds between polarized atoms play a crucial role in protein interactions and are often used in drug design, which usually neglects the potential of C-H times times times O hydrogen bonds. The 1.4 AA resolution crystal structure of the ligand binding domain of the retinoic acid receptor RAR gamma complexed with the retinoid SR11254 reveals several types of C-H times times times O hydrogen bonds. A striking example is the hydroxyl group of the ligand that acts as an H bond donor and acceptor, leading to a synergy between classical and C-H times times times O hydrogen bonds. This interaction introduces both specificity and affinity within the hydrophobic ligand pocket. The similarity of intraprotein and protein-ligand C-H times times times O interactions suggests that such bonds should be considered in rational drug design approaches.