title: A homology model of penicillin acylase from Alcaligenes faecalis and in silico evaluation of its selectivity.
abstract: A three-dimensional model of the relatively unknown penicillin acylase from Alcaligenes faecalis (PA-AF) was built up by means of homology modeling based on three different crystal structures of penicillin acylase from various sources. An in silico selectivity study was performed to compare this homology model to the structure of the Escherichia coli enzyme (PA-EC) in order to find any selectivity differences between the two enzymes. The program GRID was applied in combination with the principal component analysis technique to identify the regions of the active sites where the PAs potentially engage different interactions with ligands. These differences were further analyzed and confirmed by molecular docking simulations. The PA-AF homology model provided the structural basis for the explanation of the different enantioselectivities of the enzymes previously demonstrated experimentally and reported in the literature. Different substrate selectivities were also predicted for PA-AF compared to PA-EC. Since no crystallographic data are available for PA-AF to date, the three-dimensional homology model represents a useful and efficient tool for fully exploiting this attractive and efficient biocatalyst, particularly in enantioselective acylations of amines.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Trieste, Piazzale Europa 1, 34127 Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Braiuca
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ebert
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
authors.forename: Lucia
authors.initials: L
authors.lastname: Gardossi
authors.forename: Paolo
authors.initials: P
authors.lastname: Linda
mesh_terms: D042481:Alcaligenes faecalis / Q000201:enzymology*; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D010399:Penicillin Amidase / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D010399:Penicillin Amidase