New aspects of electron transfer revealed by the crystal structure of a truncated bovine adrenodoxin, Adx(4–108)

Muller, Alexander J.; Müller, Jürgen; Muller, Yves A.; Uhlmann, Heike; Bernhardt, Rita; Heinemann, Udo

doi:10.1016/s0969-2126(98)00031-8

Cited by 160 publications

(176 citation statements)

References 57 publications

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“…It will therefore be interesting to unravel what structural features determine the striking functional specificity of Fdx1 and Fdx2. The 3D structure of mammalian Fdx1 has already been resolved (38) and the high level of sequence similarity between Fdx1 and Fdx2 predicts similar structures. Comparative analysis of the primary structures of Fdx1 and Fdx2/Yah1 and the eventual determination of the 3D structure of Fdx2 will make it possible to understand what bestows these ferredoxins with the capacity to interact with specific substrates only.…”

Section: Discussionmentioning

confidence: 99%

Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis

Sheftel

Stehling

Pierik

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian adrenodoxin (ferredoxin 1; Fdx1) is essential for the synthesis of various steroid hormones in adrenal glands. As a member of the [2Fe-2S] cluster-containing ferredoxin family, Fdx1 reduces mitochondrial cytochrome P450 enzymes, which then catalyze; e.g., the conversion of cholesterol to pregnenolone, aldosterone, and cortisol. The high protein sequence similarity between Fdx1 and its yeast adrenodoxin homologue (Yah1) suggested that Fdx1, like Yah1, may be involved in the biosynthesis of heme A and Fe/S clusters, two versatile and essential protein cofactors. Our study, employing RNAi technology to deplete human Fdx1, did not confirm this expectation. Instead, we identified a Fdx1-related mitochondrial protein, designated ferredoxin 2 (Fdx2) and found it to be essential for heme A and Fe/S protein biosynthesis. Unlike Fdx1, Fdx2 was unable to efficiently reduce mitochondrial cytochromes P450 and convert steroids, indicating that the two ferredoxin isoforms are highly specific for their substrates in distinct biochemical pathways. Moreover, Fdx2 deficiency had a severe impact, via impaired Fe/S protein biogenesis, on cellular iron homeostasis, leading to increased cellular iron uptake and iron accumulation in mitochondria. We conclude that mammals depend on two distinct mitochondrial ferredoxins for the specific production of either steroid hormones or heme A and Fe/S proteins.adrenodoxin | cytochrome P450 | iron | iron-sulfur cluster | IRP1

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Section: Discussionmentioning

confidence: 99%

Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis

Sheftel

Stehling

Pierik

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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282

296

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“…A comparison of BenC with the related enzymes phthalate dioxygenase reductase and FNR in complex with ferredoxin revealed that the flavin and 2Fe-2S cluster can be superimposed in all three structures (39) indicating that the arrangement of the redox cofactors is highly conserved in this family of NAD(P)H dehydrogenases. We used the high-resolution structures of BenC (39) and related proteins (40,42) and Gln 112 (NqrF numbering), which in BenC are hydrogen bonded to the acid-labile sulfide S-2 of the 2Fe-2S cluster and to FIG. 7.…”

Section: Discussionmentioning

confidence: 99%

NADH Oxidation by the Na+-translocating NADH:Quinone Oxidoreductase from Vibrio cholerae

Türk

Puhar

Neese

et al. 2004

Journal of Biological Chemistry

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“…The coordinates of the Ln-Cc structure and Adx (PDB entry 1AYF (Müller et al 1998)) were used for simulations to explore the minimal sampling space required for averaging of the intermolecular RDCs. Similar to what was described before (Xu et al 2008), the relative diffusional movement of the proteins in the native complex was decomposed into two types of rotations.…”

Section: Simulation Of the Dynamicsmentioning

confidence: 99%

Intermolecular dynamics studied by paramagnetic tagging

Keizers

Reinle

et al. 2009

J Biomol NMR

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Yeast cytochrome c and bovine adrenodoxin form a dynamic electron transfer complex, which is a pure encounter complex. It is demonstrated that the dynamic nature of the interaction can readily be probed by using a rigid lanthanide tag attached to cytochrome c. The tag, Caged Lanthanide NMR Probe 5, induces pseudocontact shifts and residual dipolar couplings and does not perturb the binding interface. Due to the dynamics in the complex, residual dipolar couplings in adrenodoxin are very small. Simulation shows that cytochrome c needs to sample a large part of the surface of adrenodoxin to explain the small degree of alignment observed for adrenodoxin. The applied method provides a simple and straightforward way to observe dynamics in protein complexes or domain-domain mobility without the need for external alignment media.

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New aspects of electron transfer revealed by the crystal structure of a truncated bovine adrenodoxin, Adx(4–108)

Cited by 160 publications

References 57 publications

Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis

Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis

NADH Oxidation by the Na+-translocating NADH:Quinone Oxidoreductase from Vibrio cholerae

Intermolecular dynamics studied by paramagnetic tagging

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