title: Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: a docking and molecular dynamics study.
abstract: In the present paper, molecular modeling studies were undertaken in order to shed light on the molecular basis of the observed enantioselectivity of penicillin G acylase (PGA), a well known enzyme for its industrial applications, towards 16 racemic 2-aryloxyalkanoic acids, which have been reported to affect several biological systems. With this intention docking calculations and MD simulations were performed. Docking results indicated that the (S)-enantiomers establish several electrostatic interactions with SerB1, SerB386 and ArgB263 of PGA. Conversely, the absence of specific polar interactions between the (R)-enantiomers and ArgB263 seems to be the main reason for the different binding affinities observed between the two enantiomers. Results of molecular dynamics simulations demonstrated that polar interactions are responsible for both the ligand affinity and PGA enantiospecificity. Modeling calculations provided possible explanations for the observed enantioselectivity of the enzyme that rationalize available experimental data and could be the basis for future protein engineering efforts.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano, 49, I-80131 Napoli, Italy. lavecchi@unina.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Enrica
authors.initials: E
authors.lastname: Calleri
authors.forename: Caterina
authors.initials: C
authors.lastname: Temporini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Massolini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carbonara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fracchiolla
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
mesh_terms: D000473:Alkanes / Q000737:chemistry; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D008958:Models, Molecular; D010399:Penicillin Amidase / Q000737:chemistry* / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D000473:Alkanes; D002264:Carboxylic Acids; D012694:Serine; D001120:Arginine; D010399:Penicillin Amidase