Quantitative structure activity relationships for the electron transfer reactions ofAnabaenaPCC 7119 ferredoxin‐NADP⁺oxidoreductase with nitrobenzene and nitrobenzimidazolone derivatives: mechanistic implications

Abstract

The steady state single electron reduction of polynitroaromatics by ferredoxin-NADP + oxidoreductase (EC 1.18.1.2) from cyanobacterium Anabaena PCC 7119 has been studied and quantitative structure activity relationships are described. The solubility of the polynitroaromatics as well as their reactivity towards ferredoxin-NADP oxidoreductase are markedly higher than those for previously studied mononitroaromatics and this enabled the independent measurement of the kinetic parameters k cat and K m . Interestingly, the natural logarithm of the bimolecular rate constant, k cat /K m , and also the natural logarithm of k cat correlate with the calculated energy of the lowest unoccupied molecular orbital of the polynitroaromatic substrates. The minimal kinetic model in line with these quantitative structure activity relationships is a ping-pong mechanism which includes substrate binding equilibria in the second half reaction.z 1999 Federation of European Biochemical Societies.

QSAR Study of the Reduction of Nitroaromatics by Fe(II) Species

“…EA represents the energy difference associated with the gain of an electron (28), which should correlate with the ease or difficulty of the reduction of a compound. In addition, motivated by the fact that E LUMO has been successfully employed in toxicological studies to build QSARs for nitroaromatics (32)(33)(34), we decided to explore its potential as a molecular descriptor for nitroaromatic reduction. We expected NB reactivity to correlate with ELUMO because the latter is the energy of the molecular orbital that will contain the first gained electron in the course of reduction.…”

Effect of cadmium on ferredoxin:NADP+ oxidoreductase activity

“…It is likely that the difference between these two pathways concerns the sequences of reducing equivalent transport from FAD to the final electron acceptor. If the sequential or pingpong model of reaction mechanism is applied to FNR catalysed quinone reduction [16], Cd 2þ interfered primarily on the FNR-NADPH complex and in the step of FAD 2À oxidation.…”

“…In vitro, FNR catalyses the reduction of cytochrome c (cyt c) in the presence of NADPH and Fd. In addition, FNR is able to catalyse the NADPH-dependent reduction of many non-physiological substrates such as FeCy, methyl viologen, dichlorophenol indophenol [2,15], and polynitroamines [16,17]. The NADPH-FNR system may also be engaged in the reduction of some quinones, as DBMIB, plastoquinone-1, plastoquinone-3 [18,19].…”

Assay Technologies for Proteases

“…By sacrificing fundamental detail, however, it is nonetheless possible to obtain fairly reliably predictive computational models of enzyme kinetics by focusing directly on readily measurable rate constants such as the Michaelis constant, K M , that reflect the overall substrate processing capacity of the enzyme. Such observables can serve as the basis for the successful development of general, computationally efficient quantitative structure-activity relationship (QSAR) models (e.g., [128][129][130]). Constructing a reasonable model that accounts for substrate transport, Michaelis complex formation, and covalent reactivity requires a flexible basis of QSAR descriptors.…”