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A protein disulfide oxidoreductase from the archaeon Pyrococcus furiosus contains two thioredoxin fold units

Nature Structural Biology volume 5, pages 602–611 (1998)Cite this article

A Correction to this article was published on 01 October 1998

Abstract

Protein disulfide bond formation is a rate limiting step in protein folding and is catalyzed by enzymes belonging to the protein disulfide oxidoreductase superfamily, including protein disulfide isomerase (PDI) in eucarya and DsbA in bacteria. The first high resolution X-ray crystal structure of a protein disulfide oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus reveals structural details that suggest a relation to eukaryotic PDI. The protein consists of two homologous structural units with low sequence identity. Each unit contains a thioredoxin fold with a distinct CXXC active site motif. The accessibilities of both active sites are rather different as are, very likely, their redox properties. The protein shows the ability to catalyze the oxidation of dithiols as well as the reduction of disulfide bridges.

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Figure 1: a, Stereo ribbon diagram of pf PDO monomer.
Figure 2: a, Structure-based sequence alignment of pf PDO N- and C-units.
Figure 3: Structure-based sequence alignment of pf PDO N- and C-units with E.coli thioredoxin22 (E.coli_Trx), bacteriophage T4 glutaredoxin23 (T4_Grx), human PDI-a domain24 (Human_PDI_a), and E.coli DsbA7 (E.coli_DsbA).
Figure 4: , The final (2Fo - Fc) electron density maps at the active site regions of a, the N-unit and b, the C-unit.
Figure 5: a, The region of active site groove N.
Figure 6: Fig 6 a, The coordination geometry of the zinc binding site at the dimer interface.

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Acknowledgements

This work was supported by the European Commission project: Extremophiles as Cell Factories.

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Authors and Affiliations

  1. Center for Structural Biochemistry, Karolinska Institutet, NOVUM S-141 57, Huddinge, Sweden

    Bin Ren, Gudrun Tibbelin & Rudolf Ladenstein

  2. Dipartimento di Chimica Organica e Biologica, Università di Napoli, Via Mezzocannone 16, Napoli, 80134, Italy

    Donatella de Pascale, Mosè Rossi & Simonetta Bartolucci

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Correspondence to Rudolf Ladenstein.

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Ren, B., Tibbelin, G., de Pascale, D. et al. A protein disulfide oxidoreductase from the archaeon Pyrococcus furiosus contains two thioredoxin fold units. Nat Struct Mol Biol 5, 602–611 (1998). https://doi.org/10.1038/862

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