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Structure of the cooperative allosteric anthranilate synthase from Salmonella typhimurium

Nature Structural Biology volume 8, pages 243–247 (2001)Cite this article

Abstract

We have determined the X-ray crystal structure of the cooperative anthranilate synthase heterotetramer from Salmonella typhimurium at 1.9 Å resolution with the allosteric inhibitor l-tryptophan bound to a regulatory site in the TrpE subunit. Tryptophan binding orders a loop that in turn stabilizes the inactive T state of the enzyme by restricting closure of the active site cleft. Comparison with the structure of the unliganded, noncooperative anthranilate synthase heterotetramer from Sulfolobus solfataricus shows that the two homologs have completely different quarternary structures, even though their functional dimer pairs are structurally similar, consistent with differences in the cooperative behavior of the enzymes. The structural model rationalizes mutational and biochemical studies of the enzyme and establishes the structural differences between cooperative and noncooperative anthranilate synthase homologs.

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Figure 1: Structure of S. typhimurium anthranilate synthase.
Figure 2: The tryptophan binding site.
Figure 3: Molecular surface of the anthranilate synthase heterotetramer.
Figure 4: Comparison of the S. typhimurium (top) and S. solfataricus (bottom) heterotetramers.

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Acknowledgements

This work is based upon research conducted at the Cornell High Energy Synchrotron Light Source and the National Synchrotron Light Source at Brookhaven National Laboratory. We thank B. Sweet and the staff of beamline X12C at the NSLS for advice on MAD data collection and processing. Initial crystals were characterized in the laboratory of D. Ringe and G. Petsko at Brandeis University, and we gratefully acknowledge the resources they provided. A.A.M was supported by a National Research Service Award.

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Authors and Affiliations

  1. Department of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, 02115, Massachusetts, USA

    Anthony A. Morollo & Michael J. Eck

  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Anthony A. Morollo & Michael J. Eck

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  1. Anthony A. Morollo
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  2. Michael J. Eck
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Correspondence to Michael J. Eck.

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Morollo, A., Eck, M. Structure of the cooperative allosteric anthranilate synthase from Salmonella typhimurium. Nat Struct Mol Biol 8, 243–247 (2001). https://doi.org/10.1038/84988

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