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

Item Type:Article
Title:New aspects of electron transfer revealed by the crystal structure of a truncated bovine adrenodoxin, Adx(4-108)
Creators Name:Mueller, A. and Mueller, J.J. and Muller, Y.A. and Uhlmann, H. and Bernhardt, R. and Heinemann, U.
Abstract:BACKGROUND: Adrenodoxin (Adx) is a [2Fe-2S] ferredoxin involved in steroid hormone biosynthesis in the adrenal gland mitochondrial matrix of mammals. Adx is a small soluble protein that transfers electrons from adrenodoxin reductase (AR) to different cytochrome P450 isoforms where they are consumed in hydroxylation reactions. A crystallographic study of Adx is expected to reveal the structural basis for an important electron transfer reaction mediated by a vertebrate [2Fe-2S] ferredoxin. RESULTS: The crystal structure of a truncated bovine adrenodoxin, Adx(4-108), was determined at 1.85 A resolution and refined to a crystallographic R value of 0.195. The structure was determined using multiple wavelength anomalous dispersion phasing techniques, making use of the iron atoms in the [2Fe-2S] cluster of the protein. The protein displays the compact (alpha + beta) fold typical for [2Fe-2S] ferredoxins. The polypeptide chain is organized into a large core domain and a smaller interaction domain which comprises 35 residues, including all those previously determined to be involved in binding to AR and cytochrome P450. A small interdomain motion is observed as a structural difference between the two independent molecules in the asymmetric unit of the crystal. Charged residues of Adx(4-108) are clustered to yield a strikingly asymmetric electric potential of the protein molecule. CONCLUSIONS: The crystal structure of Adx(4-108) provides the first detailed description of a vertebrate [2Fe-2S] ferredoxin and serves to explain a large body of biochemical studies in terms of a three-dimensional structure. The structure suggests how a change in the redox state of the [2Fe-2S] cluster may be coupled to a domain motion of the protein. It seems likely that the clearly asymmetric charge distribution on the surface of Adx(4-108) and the resulting strong molecular dipole are involved in electrostatic steering of the interactions with AR and cytochrome P450.
Keywords:Adrenodoxin, Anomalous Dispersion, Crystal Structure, Cytochrome P450 System, Iron-Sulfur Cluster, Animals, Cattle
Publisher:Cell Press
Page Range:269-280
Date:15 March 1998
Official Publication:https://doi.org/10.1016/S0969-2126(98)00031-8
PubMed:View item in PubMed

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