title: Kinetic studies and molecular modelling attribute a crucial role in the specificity and stereoselectivity of penicillin acylase to the pair ArgA145-ArgB263.
abstract: Kinetic experiments with a substrate series of phenylacetyl-arylamides reveal that at least one polar group in the amine moiety is required for the proper orientation of the substrate in the large nucleophile-binding subsite of penicillin acylase of Escherichia coli. Quantum mechanical molecular modelling of enzyme-substrate interactions in the enzyme active site shows that in the case of substrates lacking local symmetry, the productive binding implies two nonsymmetrical arrangements with respect to the two positively charged guanidinium residues of ArgA145 and ArgB263. This indicates a crucial role of the specified arginine pair in the substrate- and stereoselectivity of penicillin acylase.
authors.affiliation: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Maya
authors.initials: M
authors.lastname: Guncheva
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Ivanov
authors.forename: Boris
authors.initials: B
authors.lastname: Galunsky
authors.forename: Nicolina
authors.initials: N
authors.lastname: Stambolieva
authors.forename: Jose
authors.initials: J
authors.lastname: Kaneti
mesh_terms: D000588:Amines / Q000737:chemistry; D001120:Arginine / Q000737:chemistry / Q000502:physiology*; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008958:Models, Molecular; D010399:Penicillin Amidase / Q000737:chemistry* / Q000378:metabolism*; D011789:Quantum Theory; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000588:Amines; D001120:Arginine; D010399:Penicillin Amidase