5NCH

GriE apo form

5NCH の概要

• エントリーDOI: 10.2210/pdb5nch/pdb
• 分子名称: Leucine hydroxylase (2 entities in total)
• 機能のキーワード: fe(ii)/alpha-ketoglutarate dependent dioxygenase, hydroxylase, non-heme iron protein, leucine hydroxylase, 5-hydroxyleucine, (2s4r)-5-hydroxyleucine, 4-methyl-proline, griselimycin, methyl-griselimycin, oxidoreductase
• 由来する生物種: Streptomyces sp. DSM 40835
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59728.98

構造登録者

Lukat, P.,Blankenfeldt, W.,Mueller, R. (登録日: 2017-03-05, 公開日: 2017-10-04, 最終更新日: 2024-01-17)

主引用文献

Lukat, P.,Katsuyama, Y.,Wenzel, S.,Binz, T.,Konig, C.,Blankenfeldt, W.,Bronstrup, M.,Muller, R.
Biosynthesis of methyl-proline containing griselimycins, natural products with anti-tuberculosis activity.
Chem Sci, 8:7521-7527, 2017

PubMed Abstract: Griselimycins (GMs) are depsidecapeptides with superb anti-tuberculosis activity. They contain up to three (2,4)-4-methyl-prolines (4-MePro), of which one blocks oxidative degradation and increases metabolic stability in animal models. The natural congener with this substitution is only a minor component in fermentation cultures. We showed that this product can be significantly increased by feeding the reaction with 4-MePro and we investigated the molecular basis of 4-MePro biosynthesis and incorporation. We identified the GM biosynthetic gene cluster as encoding a nonribosomal peptide synthetase and a sub-operon for 4-MePro formation. Using heterologous expression, gene inactivation, and experiments, we showed that 4-MePro is generated by leucine hydroxylation, oxidation to an aldehyde, and ring closure with subsequent reduction. The crystal structures of the leucine hydroxylase GriE have been determined in complex with substrates and products, providing insight into the stereospecificity of the reaction.

PubMed: 29163906
DOI: 10.1039/c7sc02622f

実験手法

X-RAY DIFFRACTION (1.819 Å)