Format

Send to

Choose Destination
Science. 2005 Sep 30;309(5744):2216-9.

Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination.

Author information

1
Centre for Biomolecular Sciences, EaStchem, University of St. Andrews, St. Andrews KY16 9ST, UK.

Abstract

Chlorinated natural products include vancomycin and cryptophycin A. Their biosynthesis involves regioselective chlorination by flavin-dependent halogenases. We report the structural characterization of tryptophan 7-halogenase (PrnA), which regioselectively chlorinates tryptophan. Tryptophan and flavin adenine dinucleotide (FAD) are separated by a 10 angstrom-long tunnel and bound by distinct enzyme modules. The FAD module is conserved in halogenases and is related to flavin-dependent monooxygenases. On the basis of biochemical studies, crystal structures, and by analogy with monooxygenases, we predict that FADH2 reacts with O2 to make peroxyflavin, which is decomposed by Cl-. The resulting HOCl is guided through the tunnel to tryptophan, where it is activated to participate in electrophilic aromatic substitution.

PMID:
16195462
PMCID:
PMC3315827
DOI:
10.1126/science.1116510
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center