Regulation of the mechanism of Type-II NADH: Quinone oxidoreductase from S. aureus

Filipa V. Sena, Filipe M. Sousa, A. Sofia F. Oliveira, Cláudio M. Soares, Teresa Catarino, Manuela M. Pereira*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)
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Type-II NADH:quinone oxidoreductases (NDH-2s) are membrane proteins involved in respiratory chains and the only enzymes with NADH:quinone oxidoreductase activity expressed in Staphylococcus aureus (S. aureus), one of the most common causes of clinical infections. NDH-2s are members of the two-Dinucleotide Binding Domains Flavoprotein (tDBDF) superfamily, having a flavin adenine dinucleotide, FAD, as prosthetic group and NAD(P)H as substrate. The establishment of a Charge-Transfer Complex (CTC) between the isoalloxazine ring of the reduced flavin and the nicotinamide ring of NAD+ in NDH-2 was described, and in this work we explored its role in the kinetic mechanism using different electron donors and electron acceptors. We observed that CTC slows down the rate of the second half reaction (quinone reduction) and determines the effect of HQNO, an inhibitor. Also, protonation equilibrium simulations clearly indicate that the protonation probability of an important residue for proton transfer to the active site (D302) is influenced by the presence of the CTC. We propose that CTC is critical for the overall mechanism of NDH-2 and possibly relevant to keep a low quinol/quinone ratio and avoid excessive ROS production in vivo.

Original languageEnglish
Pages (from-to)209-214
Number of pages6
JournalRedox Biology
Early online date17 Feb 2018
Publication statusPublished - 1 Jun 2018


  • FAD
  • Respiratory chain
  • Flavoprotein
  • Electron transfer
  • Bacterial respiration
  • Kinetics


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