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ToolsDong, 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
Full text not available from this repository.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 |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Depositing User: | Pure Connector |
| Date Deposited: | 17 Nov 2014 12:58 |
| Last Modified: | 20 Mar 2024 00:59 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/50986 |
| DOI: | 10.1126/science.1116510 |
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