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Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase

Nature Structural Biology volume 7, pages 303–308 (2000)Cite this article

Abstract

Here we report the first three-dimensional structure of a phosphoribosylpyrophosphate (PRPP) synthetase. PRPP is an essential intermediate in several biosynthetic pathways. Structures of the Bacillus subtilis PRPP synthetase in complex with analogs of the activator phosphate and the allosteric inhibitor ADP show that the functional form of the enzyme is a hexamer. The individual subunits fold into two domains, both of which resemble the type I phosphoribosyltransfereases. The active site is located between the two domains and includes residues from two subunits. Phosphate and ADP bind to the same regulatory site consisting of residues from three subunits of the hexamer. In addition to identifying residues important for binding substrates and effectors, the structures suggest a novel mode of allosteric regulation.

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Figure 1: Alignment of PRPP synthetase sequences
Figure 2: Overall fold, topology and quaternary structure of PRPP synthetase
Figure 3: Catalytic and regulatory sites with omit electron density maps
Figure 4: Stereo views of the catalytic and regulatory sites

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Acknowledgements

Support from the Danish National Research Foundation is gratefully acknowledged. We are grateful to the EMBL Hamburg outstation DESY for beam time and thank W. Rypniewski for his help during the experiments.

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Author notes

  1. Kenneth W. Harlow

    Present address: Zealand Pharmaceuticals, Smedeland 26 B, DK-2600, Glostrup, Denmark

Authors and Affiliations

  1. Department of Chemistry, Center for Crystallographic Studies, University of Copenhagen, Universitetsparken 5, Copenhagen, DK-2100, Denmark

    Tine A. Eriksen, Anders Kadziola & Sine Larsen

  2. Center for Enzyme Research, Institute of Molecular Biology, University of Copenhagen, Sølvgade 83H, Copenhagen, DK-1307, Denmark

    Ann-Kristin Bentsen & Kenneth W. Harlow

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  1. Tine A. Eriksen
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  5. Sine Larsen
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Correspondence to Sine Larsen.

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Eriksen, T., Kadziola, A., Bentsen, AK. et al. Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase. Nat Struct Mol Biol 7, 303–308 (2000). https://doi.org/10.1038/74069

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