title: Biological chiral recognition: the substrate's perspective.
abstract: A novel stereocenter-recognition (SR) model has been proposed recently for describing the stereoselectivity of biological and other macromolecules towards substrates that have multiple stereocenters, based on the topology of substrate stereocenters (Sundaresan and Abrol, Prot Sci 11:1330-1339, 2002). The SR model provides the minimum number of substrate locations interacting with receptor sites that need to be considered for understanding stereoselectivity characteristics. Interactions between substrate locations and receptor sites may be binding, nonbinding or repulsive in nature and may occur in a many-to-one or one-to-many fashion, but for a receptor to be stereoselective, its interactions with substrate stereoisomers have to involve a minimum number of locations, in the correct geometry. The SR model is topologically rigorous, explains several previous experimental observations, and is predictive in nature. It predicts that stereoselectivity towards a substrate with N stereocenters in a linear structure involves a minimum of N + 2 substrate locations, distributed over all stereocenters in the substrate, such that effectively at least three locations per stereocenter interact with one or more receptor sites. This article uses the SR model to provide an insight into the chiral recognition process from a substrate's perspective that is intuitive and simple, furnishing a rigorous stereochemical basis for explaining stereoselectivity characteristics of many biological systems.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. vidya@scripps.edu
authors.forename: Vidyasankar
authors.initials: V
authors.lastname: Sundaresan
authors.forename: Ravinder
authors.initials: R
authors.lastname: Abrol
mesh_terms: D020346:Aquaporins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D043422:Carboxypeptidases A / Q000037:antagonists & inhibitors / Q000737:chemistry; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010650:Phenylalanine Ammonia-Lyase / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011942:Receptors, Adrenergic, alpha / Q000737:chemistry / Q000378:metabolism; D012255:Ribitol / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D013402:Sugar Alcohols / Q000378:metabolism
chemical_list: D020346:Aquaporins; D004798:Enzymes; D029968:Escherichia coli Proteins; D011942:Receptors, Adrenergic, alpha; D013402:Sugar Alcohols; C078043:GlpF protein, E coli; D012255:Ribitol; D007521:Isocitrate Dehydrogenase; D043422:Carboxypeptidases A; D010650:Phenylalanine Ammonia-Lyase; C014999:arabitol