5HY5

Crystal Structure of a Tryptophan 6-halogenase (SttH) from Streptomyces toxytricini

5HY5 の概要

• エントリーDOI: 10.2210/pdb5hy5/pdb
• 分子名称: Tryptophan 6-halogenase, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: tryptophan halogenase, oxidoreductase
• 由来する生物種: Streptomyces toxytricini
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 119218.25

構造登録者

Levy, C. (登録日: 2016-02-01, 公開日: 2016-02-17, 最終更新日: 2024-05-01)

主引用文献

Shepherd, S.A.,Menon, B.R.,Fisk, H.,Struck, A.W.,Levy, C.,Leys, D.,Micklefield, J.
A Structure-Guided Switch in the Regioselectivity of a Tryptophan Halogenase.
Chembiochem, 17:821-824, 2016

PubMed Abstract: Flavin-dependent halogenases are potentially useful biocatalysts for the regioselective halogenation of aromatic compounds. Haloaromatic compounds can be utilised in the synthesis and biosynthesis of pharmaceuticals and other valuable products. Here we report the first X-ray crystal structure of a tryptophan 6-halogenase (SttH), which enabled key residues that contribute to the regioselectivity in tryptophan halogenases to be identified. Structure-guided mutagenesis resulted in a triple mutant (L460F/P461E/P462T) that exhibited a complete switch in regioselectivity; with the substrate 3-indolepropionate 75 % 5-chlorination was observed with the mutant in comparison to 90 % 6-chlorination for the wild-type SttH. This is the first clear example of how regiocomplementary halogenases can be created from a single parent enzyme. The biocatalytic repertoire of SttH was also expanded to include a range of indolic and non-indolic substrates.

PubMed: 26840773
DOI: 10.1002/cbic.201600051

実験手法

X-RAY DIFFRACTION (2.68 Å)