Tryptophan 7-Halogenase (PrnA) Structure Suggests a Mechanism for Regioselective Chlorination

C Dong, S Flecks, S Unversucht, C Haupt, K-H Van Pee, James Henderson Naismith

Research output: Contribution to journalArticlepeer-review

319 Citations (Scopus)

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 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 FADH(2) reacts with O-2 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.

Original languageEnglish
Pages (from-to)2216-2219
Number of pages4
JournalScience
Volume309
Issue number5744
DOIs
Publication statusPublished - 30 Sept 2005

Keywords

  • BIOSYNTHETIC GENE-CLUSTER
  • PARA-HYDROXYBENZOATE HYDROXYLASE
  • CATION-PI INTERACTIONS
  • PSEUDOMONAS-FLUORESCENS
  • CHLOROPEROXIDASE
  • STREPTOMYCES
  • HALOGENATION
  • PYRROLNITRIN
  • REBECCAMYCIN
  • DERIVATIVES

Fingerprint

Dive into the research topics of 'Tryptophan 7-Halogenase (PrnA) Structure Suggests a Mechanism for Regioselective Chlorination'. Together they form a unique fingerprint.

Cite this