title: C-H...O hydrogen bonds in the nuclear receptor RARgamma--a potential tool for drug selectivity.
abstract: 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...O hydrogen bonds. The 1.4 A resolution crystal structure of the ligand binding domain of the retinoic acid receptor RARgamma complexed with the retinoid SR11254 reveals several types of C-H...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...O hydrogen bonds. This interaction introduces both specificity and affinity within the hydrophobic ligand pocket. The similarity of intraprotein and protein-ligand C-H...O interactions suggests that such bonds should be considered in rational drug design approaches.
authors.affiliation: Laboratoire de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 rue Laurent Fries, BP 163, F-67404 Illkirch Cédex, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Klaholz
authors.forename: Dino
authors.initials: D
authors.lastname: Moras
mesh_terms: D002244:Carbon / Q000378:metabolism; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000097768:Retinoic Acid Receptor gamma
chemical_list: D002244:Carbon; D008024:Ligands; D010100:Oxygen; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma