5JGK

Crystal structure of GtmA in complex with SAH

5JGK の概要

• エントリーDOI: 10.2210/pdb5jgk/pdb
• 分子名称: UbiE/COQ5 family methyltransferase, putative, S-ADENOSYL-L-HOMOCYSTEINE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: aspergillus fumigatus, methyltransferase, s-adenosyl-l-homocysteine, gliotoxin, resistance, transferase
• 由来する生物種: Aspergillus fumigatus Z5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66160.96

構造登録者

Dolan, S.K.,Bock, T.,Hering, V.,Jones, G.W.,Blankenfeldt, W.,Dolye, S. (登録日: 2016-04-20, 公開日: 2017-03-01, 最終更新日: 2024-05-08)

主引用文献

Dolan, S.K.,Bock, T.,Hering, V.,Owens, R.A.,Jones, G.W.,Blankenfeldt, W.,Doyle, S.
Structural, mechanistic and functional insight into gliotoxinbis-thiomethylation inAspergillus fumigatus.
Open Biol, 7:-, 2017

PubMed Abstract: Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin -methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to -adenosylhomocysteine (1.33 Å) and GtmA complexed to -adenosylmethionine (2.28 Å), providing mechanistic insights into this important biotransformation. We further reveal that simultaneous elimination of the ability of to dissipate highly reactive dithiol gliotoxin, via deletion of GliT and GtmA, results in the most significant hypersensitivity to exogenous gliotoxin observed to date. Indeed, quantitative proteomic analysis of Δ::Δ reveals an uncontrolled over-activation of the -cluster upon gliotoxin exposure. The data presented herein reveal, for the first time, the extreme risk associated with intracellular dithiol gliotoxin biosynthesis-in the absence of an efficient dismutation capacity. Significantly, a previously concealed protective role for GtmA and functionality of ETP -thiomethylation as an ancestral protection strategy against dithiol compounds is now evident.

PubMed: 28179499
DOI: 10.1098/rsob.160292

実験手法

X-RAY DIFFRACTION (1.33 Å)