Regulation of the mechanism of Type-II NADH: Quinone oxidoreductase from S. aureus
| Autor: | A. Sofia F. Oliveira, Cláudio M. Soares, Teresa Catarino, Manuela M. Pereira, Filipa V. Sena, Filipe M. Sousa |
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| Přispěvatelé: | Molecular, Structural and Cellular Microbiology (MOSTMICRO), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), DQ - Departamento de Química |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus Stereochemistry Clinical Biochemistry Respiratory chain Flavoprotein Flavin group Biochemistry Cofactor Substrate Specificity Electron Transport Electron transfer 03 medical and health sciences chemistry.chemical_compound Catalytic Domain NAD(P)H Dehydrogenase (Quinone) lcsh:QH301-705.5 Flavin adenine dinucleotide lcsh:R5-920 Binding Sites 030102 biochemistry & molecular biology biology FAD Organic Chemistry Quinones Active site 3. Good health Quinone Kinetics 030104 developmental biology Bacterial respiration chemistry lcsh:Biology (General) Flavin-Adenine Dinucleotide biology.protein NAD+ kinase Reactive Oxygen Species lcsh:Medicine (General) Research Paper |
| Zdroj: | Redox Biology, Vol 16, Iss, Pp 209-214 (2018) Redox Biology Sena, F V, Sousa, F M, Oliveira, A S F, Soares, C M, Catarino, T & Pereira, M M 2018, ' Regulation of the mechanism of Type-II NADH : Quinone oxidoreductase from S. aureus ', Redox Biology, vol. 16, pp. 209-214 . https://doi.org/10.1016/j.redox.2018.02.004 Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 2213-2317 |
| Popis: | 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. Graphical abstract fx1 |
| Databáze: | OpenAIRE |
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