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 journalArticlepeer-review

100 Scopus citations


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
Issue number8
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Structural basis for halogenation by iron-and 2-oxo-glutarate-dependent enzyme WelO5'. Together they form a unique fingerprint.

Cite this