Letter | Published:

Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis

Nature volume 440, pages 368371 (16 March 2006) | Download Citation



Non-haem Fe(ii)/α-ketoglutarate (αKG)-dependent enzymes harness the reducing power of αKG to catalyse oxidative reactions, usually the hydroxylation of unactivated carbons, and are involved in processes such as natural product biosynthesis, the mammalian hypoxic response, and DNA repair1,2. These enzymes couple the decarboxylation of αKG with the formation of a high-energy ferryl-oxo intermediate that acts as a hydrogen-abstracting species2,3,4. All previously structurally characterized mononuclear iron enzymes contain a 2-His, 1-carboxylate motif that coordinates the iron1,2. The two histidines and one carboxylate, known as the ‘facial triad’, form one triangular side of an octahedral iron coordination geometry. A subclass of mononuclear iron enzymes has been shown to catalyse halogenation reactions, rather than the more typical hydroxylation reaction5,6. SyrB2, a member of this subclass, is a non-haem Fe(ii)/αKG-dependent halogenase that catalyses the chlorination of threonine in syringomycin E biosynthesis5. Here we report the structure of SyrB2 with both a chloride ion and αKG coordinated to the iron ion at 1.6 Å resolution. This structure reveals a previously unknown coordination of iron, in which the carboxylate ligand of the facial triad is replaced by a chloride ion.

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We thank J. W. Nix and T. Doukov for help with data collection; and M. Fischbach for critically reading the manuscript. The Advanced Light Source and Stanford Synchrotron Radiation Laboratory are supported by the US Department of Energy. The SSRL Structural Molecular Biology Program is also supported by the National Institutes of Health. This work was supported in part by grants from the NIH (to C.L.D., to C.T.W. and to L.C.B.), a Merck-sponsored Fellowship of the Helen Hay Whitney Foundation (to F.H.V.) and a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship (to F.H.V.).

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Author notes

    • Frédéric H. Vaillancourt

    †Present address: Department of Biological Sciences, Research and Development, Boehringer Ingelheim (Canada) Ltd, Laval, Quebec H7S 2G5, Canada


  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Leah C. Blasiak
    •  & Catherine L. Drennan
  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Frédéric H. Vaillancourt
    •  & Christopher T. Walsh


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Competing interests

The coordinates and structure factors for αKG–SyrB2, Cl–Fe(ii)–αKG–SyrB2 and Br–Fe(ii)–αKG–SyrB2 have been deposited in the Protein Data Bank with accession codes 2FCT, 2FCU and 2FCV, respectively. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Catherine L. Drennan.

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    Supplementary Notes

    This file contains Supplementary Figures 1–4, Supplementary Methods and Supplementary Table 1.

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