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

Nat Chem Biol. 2016 Aug;12(8):636-40. doi: 10.1038/nchembio.2112. Epub 2016 Jun 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Crystallography, X-Ray
  • Glutarates / metabolism*
  • Halogenation*
  • Iron / metabolism*
  • Models, Molecular
  • Molecular Structure
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism*

Substances

  • Glutarates
  • Iron
  • Oxidoreductases

Associated data

  • PubChem-Substance/313389844
  • PubChem-Substance/313389845
  • PubChem-Substance/313389846