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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination
Changjiang Dong1, Silvana Flecks, Susanne Unversucht
1Centre 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.
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