title: Structural basis for halogenation by iron- and 2-oxo-glutarate-dependent enzyme WelO5.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mitchell
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Ailiena O
authors.initials: AO
authors.lastname: Maggiolo
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Nikhil R
authors.initials: NR
authors.lastname: Ananth
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hillwig
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.|Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Amie K
authors.initials: AK
authors.lastname: Boal
mesh_terms: D018360:Crystallography, X-Ray; D005977:Glutarates / Q000378:metabolism*; D054879:Halogenation; D007501:Iron / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005977:Glutarates; D007501:Iron; D010088:Oxidoreductases