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

Dong, Changjiang, Flecks, Silvana, Unversucht, Susanne, Haupt, Caroline, van Pée, Karl-Heinz and Naismith, James H (2005) Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination. Science, 309 (5744). pp. 2216-9. ISSN 0036-8075

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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.

Item Type: Article
Uncontrolled Keywords: amino acid sequence,binding sites,chlorides,crystallography, x-ray,dimerization,flavin-adenine dinucleotide,hydrogen bonding,hypochlorous acid,indoles,models, molecular,molecular sequence data,oxidation-reduction,oxidoreductases,oxygen,protein conformation,protein structure, secondary,protein structure, tertiary,pseudomonas fluorescens,tryptophan
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 17 Nov 2014 12:58
Last Modified: 21 Apr 2020 23:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/50986
DOI: 10.1126/science.1116510

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