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

FEBS Letters

Segura-Aguilar, Juan²  Anusevicius, Zilvinas³  Cénas, Narimantas¹  Soffers, Ans E.M.F³  Sarlauskas, Jonas¹  Rietjens, Ivonne M.C.M³ 

[1] Institute of Biochemistry, Mokslininku 12, Vilnius 2600, Lithuania;Unit of Biochemical Toxicology, Wallenberg Laboratory, Department of Biochemistry, Stockholm University, Stockholm, Sweden;Department of Biomolecular Sciences, Laboratory of Biochemistry, Agricultural University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands

关键词: DT-diaphorase;    Nitrobenzimidazol(on)e;    Kinetic model;    Quantitative structure activity relationship;    Energy of lowest unoccupied molecular orbital;   

DOI  :  10.1016/S0014-5793(98)00456-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown