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

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-Dinucl...

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Bibliographic Details
Published in:Redox biology 2018-06, Vol.16, p.209-214
Main Authors: Sena, Filipa V., Sousa, Filipe M., Oliveira, A. Sofia F., Soares, Cláudio M., Catarino, Teresa, Pereira, Manuela M.
Format: Article
Language:English
Subjects:
Bacterial respiration
Binding Sites
Catalytic Domain
Electron transfer
Electron Transport
FAD
Flavin-Adenine Dinucleotide - chemistry
Flavin-Adenine Dinucleotide - metabolism
Flavoprotein
Kinetics
NAD(P)H Dehydrogenase (Quinone) - chemistry
NAD(P)H Dehydrogenase (Quinone) - metabolism
Quinones - chemistry
Quinones - metabolism
Reactive Oxygen Species - chemistry
Reactive Oxygen Species - metabolism
Research Paper
Respiratory chain
Staphylococcus aureus - enzymology
Staphylococcus aureus - pathogenicity
Substrate Specificity
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Summary: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. [Display omitted]
ISSN:2213-2317
2213-2317
DOI:10.1016/j.redox.2018.02.004