The receptor concept in 3D: from hypothesis and metaphor to GPCR-ligand structures.

摘要: The first mentioning of the word “receptor” for structure with which a bioactive compound should react obtaining its specific influence on physiological system goes back to years around 1900. receptor concept was adapted from lock and key theory enzyme substrate blockers interactions. Through concept, in beginning rather being metaphor, not model, refined became reality recent years. Not only structures receptors were elucidated, also machineries unraveled. Following brief historical review we will describe how breakthroughs experimental determination G protein-coupled (GPCR) crystal can be complemented by computational modeling, medicinal chemistry, biochemical, molecular pharmacological studies obtain new insights into determinants GPCR–ligand binding activation. We furthermore discuss this information used structure-based discovery novel GPCR ligands that bind (allosteric) sites desired effects functional activity.