title: Protonation state of Asp120 in the binuclear active site of the metallo-beta-lactamase from Bacteroides fragilis.
abstract: The determination of the protonation state of enzyme active sites may be crucial for the investigation of their mechanism of action. In the bizinc beta-lactamase family of enzymes, no consensus has been reached on the protonation state of a fully conserved amino acid present in the active site, Asp120. To address this issue, we carry out here density functional theory (DFT) calculations on large models (based on Bacteroides fragilis X-ray structure) which include the metal coordination polyhedron and groups interacting with it. Our calculations suggest that Asp120 is ionized. The relevance of this finding for site-directed mutagenesis experiments on the 120 position and on the mechanism of action is discussed.
authors.affiliation: International School for Advanced Studies, SISSA and INFM-DEmocritos MOdeling Center for Research in aTOmistic Simulation, via Beirut 2-4, 34014 Trieste, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dal Peraro
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Vila
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001224:Aspartic Acid / Q000737:chemistry*; D001441:Bacteroides fragilis / Q000201:enzymology*; D001665:Binding Sites; D002384:Catalysis; D019295:Computational Biology; D008958:Models, Molecular; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed; D011522:Protons; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics
chemical_list: D011522:Protons; D001224:Aspartic Acid; D001618:beta-Lactamases