title: Determination of the catalytic pathway of a manganese arginase enzyme through density functional investigation.
abstract: The catalytic mechanism of dimanganese-containing arginase enzyme has been investigated by DFT calculations. Two exchange-correlation functionals, B3 LYP and MPWB1 K, have been used to construct the potential energy profiles for the hydrolysis of an arginine substrate performed by an arginase active site model system. Two reaction mechanisms have been investigated, one involving a water molecule (mechanism 1) and the other involving a hydroxide ion (mechanism 2) as nucleophilic agent. Results obtained in the gas phase and in the protein environment have indicated that mechanism 1 involving a water molecule entails structural features as well as an activation energy for the rate-determining step that are inconsistent with experimental data available for the arginase enzyme. On the other hand, when a hydroxide ion is present at the Mn2 site, a lower activation energy and a structural arrangement closer to the experimental indication are obtained.
authors.affiliation: Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d'Eccellenza MIUR, Universita' della Calabria, 87030 Arcavacata di Rende (CS) (Italy), Fax: (+39)0984-493390.
authors.forename: Monica
authors.initials: M
authors.lastname: Leopoldini
authors.affiliation: Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d'Eccellenza MIUR, Universita' della Calabria, 87030 Arcavacata di Rende (CS) (Italy), Fax: (+39)0984-493390.
authors.forename: Nino
authors.initials: N
authors.lastname: Russo
authors.affiliation: Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d'Eccellenza MIUR, Universita' della Calabria, 87030 Arcavacata di Rende (CS) (Italy), Fax: (+39)0984-493390.
authors.forename: Marirosa
authors.initials: M
authors.lastname: Toscano
mesh_terms: D000818:Animals; D001119:Arginase / Q000737:chemistry* / Q000378:metabolism*; D001407:Bacillus / Q000201:enzymology; D001665:Binding Sites; D002384:Catalysis; D008099:Liver / Q000201:enzymology; D008345:Manganese / Q000737:chemistry*; D008954:Models, Biological; D015394:Molecular Structure; D051381:Rats; D013379:Substrate Specificity; D013816:Thermodynamics; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D008345:Manganese; D001119:Arginase