title: Promiscuous ability of human carbonic anhydrase: QM and QM/MM investigation of carbon dioxide and carbodiimide hydration.
abstract: The hydration of carbodiimide, isoelectronic with carbon dioxide, mediated by human carbonic anhydrase (EC 4.2.1.1) was studied at theoretical level in comparison with the native substrate. Quantum-mechanical (QM) and combined quantum-mechanics/molecular-mechanics (QM/MM) approaches indicate that human carbonic anhydrase is able to catalyze also the hydration of carbodiimide to urea with an energy barrier higher than that required by the native CO2. The rate-determining step for both substrates is represented by the nucleophilic addition to the double bond, showing the final product ureate more strongly anchored to the enzyme active site than the hydrogen carbonate. The reduced catalytic activity for the carbodiimide substrate can be ascribed not only to the highest barrier but also to the difficulty in releasing the product in favor of the water molecule, delaying the catalytic turnover as indicated by QM and QM/MM analyses.
authors.affiliation: Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria , 87036 Rende CS, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Piazzetta
authors.forename: Tiziana
authors.initials: T
authors.lastname: Marino
authors.forename: Nino
authors.initials: N
authors.lastname: Russo
mesh_terms: D002245:Carbon Dioxide / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D006801:Humans; D007094:Imides / Q000737:chemistry*; D008958:Models, Molecular; D011789:Quantum Theory; D014867:Water / Q000737:chemistry
chemical_list: D007094:Imides; D014867:Water; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases