Molecular mechanism of metabolic NAD(P)H-dependent electron-transfer systems: The role of redox cofactors |
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Authors: | Takashi Iyanagi |
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Affiliation: | Department of Life Science, Graduate School of Life Science, University of Hyogo, Koto 3-2-1, Kamighori, Ako, Hyogo 678-1297, Japan |
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Abstract: | NAD(P)H-dependent electron-transfer (ET) systems require three functional components: a flavin-containing NAD(P)H-dehydrogenase, one-electron carrier and metal-containing redox center. In principle, these ET systems consist of one-, two- and three-components, and the electron flux from pyridine nucleotide cofactors, NADPH or NADH to final electron acceptor follows a linear pathway: NAD(P)H?→?flavin?→?one-electron carrier?→?metal containing redox center. In each step ET is primarily controlled by one- and two-electron midpoint reduction potentials of protein-bound redox cofactors in which the redox-linked conformational changes during the catalytic cycle are required for the domain-domain interactions. These interactions play an effective ET reactions in the multi-component ET systems. The microsomal and mitochondrial cytochrome P450 (cyt P450) ET systems, nitric oxide synthase (NOS) isozymes, cytochrome b5 (cyt b5) ET systems and methionine synthase (MS) ET system include a combination of multi-domain, and their organizations display similarities as well as differences in their components. However, these ET systems are sharing of a similar mechanism. More recent structural information obtained by X-ray and cryo-electron microscopy (cryo-EM) analysis provides more detail for the mechanisms associated with multi-domain ET systems. Therefore, this review summarizes the roles of redox cofactors in the metabolic ET systems on the basis of one-electron redox potentials. In final Section, evolutionary aspects of NAD(P)H-dependent multi-domain ET systems will be discussed. |
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Keywords: | ET electron-transfer Fl oxidized flavin ? anionic fully reduced flavin 2 neutral fully reduced flavin ? anionic flavin semiquinone ? neutral flavin semiquinone ? hydride ion transfer Fdx ferredoxin Adx adrenodoxin Fldx flavodoxin ox/sq oxidized (ox)-semiquinone (sq) couple one-electron reduction potential sq/red semiquinone (sq)-fully reduced (red) couple one-electron reduction potential FNR + CYP cytochrome P450 MS reductase methione synthase reductase NOS nitric oxide synthase nNOS neuronal NOS eNOS endothelial NOS iNOS inducible NOS P450BM3 bacteria cytochrome P450BM3 cryo-EM cryo electron microscopy CaM calmodulin HGT horizontal gene transfer ER endoplasmic reticulum EPR electron paramagnetic resonance NAD(P)H-dependent electron-transfer systems Flavoenzymes Redox potentials Catalytic cycle Cytochrome P450 reductase Nitric oxide synthase |
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