title: Quantitative structure activity relationships for the conversion of nitrobenzimidazolones and nitrobenzimidazoles by DT-diaphorase: implications for the kinetic mechanism.
abstract: Quantitative structure activity relationships (QSARs) for the conversion of nitrobenzimidazolones and nitrobenzimidazoles by rat liver DT-diaphorase (EC 1.6.99.2) are described. The parameter used for description of the QSARs is the energy of the lowest unoccupied molecular orbital (E(LUMO)) of the nitroaromatic compounds. Interestingly, correlations with E(LUMO) were observed for both the natural logarithm of kcat, but also for the natural logarithm of kcat/Km. The minimal kinetic model in line with these QSARs is a ping-pong mechanism that includes a substrate binding equilibrium in the second half reaction.
authors.affiliation: Department of Biomolecular Sciences, Laboratory of Biochemistry, Agricultural University, The Netherlands.
authors.forename: Z
authors.initials: Z
authors.lastname: Anusevicius
authors.forename: A E
authors.initials: AE
authors.lastname: Soffers
authors.forename: N
authors.initials: N
authors.lastname: Cénas
authors.forename: J
authors.initials: J
authors.lastname: Sarlauskas
authors.forename: J
authors.initials: J
authors.lastname: Segura-Aguilar
authors.forename: I M
authors.initials: IM
authors.lastname: Rietjens
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D016014:Linear Models; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D011789:Quantum Theory; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D016660:NAD(P)H Dehydrogenase (Quinone)