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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Mitchell AJ,Zhu Q,Maggiolo AO,Ananth NR,Hillwig ML,Liu X,Boal AKdoi
10.1038/nchembio.2112subject
Has Abstractpub_date
2016-08-01 00:00:00pages
636-40issue
8eissn
1552-4450issn
1552-4469pii
nchembio.2112journal_volume
12pub_type
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