Structural basis for halogenation by iron-and 2-oxo-glutarate-dependent enzyme WelO5

Andrew J. Mitchell, Qin Zhu, Ailiena O. Maggiolo, Nikhil R. Ananth, Matthew L. Hillwig, Xinyu Liu, Amie K. Boal

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

A 2.4-Å-resolution X-ray crystal structure of the carrier-protein-independent halogenase WelO5 in complex with its welwitindolinone precursor substrate, 12-epi-fischerindole U, reveals that the C13 chlorination target is proximal to the anticipated site of the oxo group in a presumptive cis-halo-oxo-iron(IV) (haloferryl) intermediate. Prior study of related halogenases forecasts substrate hydroxylation in this active-site configuration, but X-ray crystallographic verification of C13 halogenation in single crystals mandates that ligand dynamics must reposition the oxygen ligand to enable the observed outcome. S189A WelO5 produces a mixture of halogenation and hydroxylation products, showing that an outer-sphere hydrogen-bonding group orchestrates ligand movements to achieve a configuration that promotes halogen transfer.

Original languageEnglish (US)
Pages (from-to)636-640
Number of pages5
JournalNature Chemical Biology
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Mitchell, A. J., Zhu, Q., Maggiolo, A. O., Ananth, N. R., Hillwig, M. L., Liu, X., & Boal, A. K. (2016). Structural basis for halogenation by iron-and 2-oxo-glutarate-dependent enzyme WelO5. Nature Chemical Biology, 12(8), 636-640. https://doi.org/10.1038/nchembio.2112