Quantitative structure activity relationships for the conversion of nitrobenzimidazolones and nitrobenzimidazoles by DT-diaphorase: implications for the kinetic mechanism

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...

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Bibliographic Details
Published in:FEBS letters 1998-05, Vol.427 (3), p.325-329
Main Authors: Anusevicius, Zilvinas, Soffers, Ans E.M.F, Cénas, Narimantas, Sarlauskas, Jonas, Segura-Aguilar, Juan, Rietjens, Ivonne M.C.M
Format: Article
Language:English
Subjects:
Animals
Benzimidazoles - chemistry
Benzimidazoles - metabolism
Biochemie
Biochemistry
DT-diaphorase
Energy of lowest unoccupied molecular orbital
Kinetic model
Kinetics
Linear Models
Liver - enzymology
Models, Molecular
NAD(P)H Dehydrogenase (Quinone) - metabolism
Nitrobenzimidazol(on)e
Quantitative structure activity relationship
Quantum Theory
Rats
Structure-Activity Relationship
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Summary: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 k cat, but also for the natural logarithm of k cat/ K m. 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.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(98)00456-6