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Analyzing protein functions in four dimensions

Nature Structural Biology volume 7, pages 1006–1012 (2000)Cite this article

Abstract

Time-resolved structural studies on biomolecular function are coming of age. Focus has shifted from studies on 'systems of opportunities' to a more problem-oriented approach, addressing significant questions in biology and chemistry. An important step in this direction has been the use of physical and chemical trapping methods to capture and then freeze reaction intermediates in crystals. Subsequent monochromatic data collection at cryogenic temperatures can produce high resolution structures of otherwise elusive intermediates. The combination of diffraction methods with spectroscopic techniques provides a means to directly correlate electronic transitions with structural transitions in the sample, eliminating much of the guesswork from experiments. Studies on cytochrome P450, isopenicillin N synthase, cytochrome cd1 nitrite reductase, copper amine oxidase and bacteriorhodopsin were selected as examples, and the results are discussed.

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Figure 1: The c-type cytochrome domain of cytochrome cd1 in three different states24.
Figure 2: First view of a bound dioxygen species at a copper center25.
Figure 3: The reaction cycle of cytochrome P450cam.
Figure 4: Light-induced structural changes during the photocycle of bacteriorhodpsins.

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Acknowledgements

This work was supported by the Swedish Research Councils, the EU-Biotech Programme STINT, EMBO and the BBSRC Structural Biology Initiative.

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Authors and Affiliations

  1. Department of Biochemistry, Uppsala University, Biomedical Center, Box 576, Uppsala, S-751 23, Sweden

    Janos Hajdu, Richard Neutze, Tove Sjögren, Karl Edman & Abraham Szöke

  2. The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, South Parks Road, Oxford, OX1 3QY, UK

    Rupert C. Wilmouth

  3. Astbury Centre for Structural Molecular Biology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK

    Carrie M. Wilmot

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  1. Janos Hajdu
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Correspondence to Janos Hajdu or Carrie M. Wilmot.

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Hajdu, J., Neutze, R., Sjögren, T. et al. Analyzing protein functions in four dimensions. Nat Struct Mol Biol 7, 1006–1012 (2000). https://doi.org/10.1038/80911

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