2AR8

The structure of tryptophan 7-halogenase (PrnA)suggests a mechanism for regioselective chlorination

Summary for 2AR8

• Entry DOI: 10.2210/pdb2ar8/pdb
• Related: 2APG 2AQJ
• Descriptor: tryptophan halogenase PrnA, CHLORIDE ION, 7-CHLOROTRYPTOPHAN, ... (5 entities in total)
• Functional Keywords: tryptophan 7-halogenase, flavin-dependent halogenase, helical bundle, sandwiched sheets, structural genomics, scottish structural proteomics facility, sspf, biosynthetic protein
• Biological source: Pseudomonas fluorescens
• Total number of polymer chains: 1
• Total formula weight: 62205.76

Authors

Dong, C.,Flecks, S.,Unversucht, S.,Haupt, C.,Van Pee, K.H.,Naismith, J.H.,Scottish Structural Proteomics Facility (SSPF) (deposition date: 2005-08-19, release date: 2005-10-04, Last modification date: 2023-11-15)

Primary citation

Dong, C.,Flecks, S.,Unversucht, S.,Haupt, C.,van Pee, K.H.,Naismith, J.H.
Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination.
Science, 309:2216-2219, 2005

PubMed 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.

PubMed: 16195462
DOI: 10.1126/science.1116510

Experimental method

X-RAY DIFFRACTION (2.2 Å)