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

被引：303

作者：

Dong, CJ

Flecks, S

Unversucht, S

Haupt, C

van Pée, KH

Naismith, JH ^{[1
]}

机构：

[1] Univ St Andrews, EaStchem, Ctr Biomol Sci, St Andrews KY16 9ST, Fife, Scotland

[2] Tech Univ Dresden, Inst Biochem, D-01062 Dresden, Germany

来源：

SCIENCE | 2005年 / 309卷 / 5744期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1126/science.1116510

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：2216 / 2219

页数：4

共 36 条

[31] COMPARISON OF THE 3-DIMENSIONAL PROTEIN AND NUCLEOTIDE STRUCTURE OF THE FAD-BINDING DOMAIN OF PARA-HYDROXYBENZOATE HYDROXYLASE WITH THE FAD-BINDING AS WELL AS NADPH-BINDING DOMAINS OF GLUTATHIONE-REDUCTASE [J].