6XP8

The crystal structure of TfuA involved in peptide backbone thioamidation from Methanosarcina acetivorans

6XP8 の概要

• エントリーDOI: 10.2210/pdb6xp8/pdb
• 分子名称: TfuA domain-containing protein (2 entities in total)
• 機能のキーワード: ycao, tfua, thioamidation, biosynthetic protein
• 由来する生物種: Methanosarcina acetivorans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23887.32

構造登録者

Dong, S.-H.,Nair, S.K. (登録日: 2020-07-08, 公開日: 2021-03-17, 最終更新日: 2024-03-06)

主引用文献

Liu, A.,Si, Y.,Dong, S.H.,Mahanta, N.,Penkala, H.N.,Nair, S.K.,Mitchell, D.A.
Functional elucidation of TfuA in peptide backbone thioamidation.
Nat.Chem.Biol., 17:585-592, 2021

PubMed Abstract: YcaO enzymes catalyze several post-translational modifications on peptide substrates, including thioamidation, which substitutes an amide oxygen with sulfur. Most predicted thioamide-forming YcaO enzymes are encoded adjacent to TfuA, which when present, is required for thioamidation. While activation of the peptide amide backbone is well established for YcaO enzymes, the function of TfuA has remained enigmatic. Here we characterize the TfuA protein involved in methyl-coenzyme M reductase thioamidation and demonstrate that TfuA catalyzes the hydrolysis of thiocarboxylated ThiS (ThiS-COSH), a proteinaceous sulfur donor, and enhances the affinity of YcaO toward the thioamidation substrate. We also report a crystal structure of a TfuA, which displays a new protein fold. Our structural and mutational analyses of TfuA have uncovered conserved binding interfaces with YcaO and ThiS in addition to revealing a hydrolase-like active site featuring a Ser-Lys catalytic pair.

PubMed: 33707784
DOI: 10.1038/s41589-021-00771-0

実験手法

X-RAY DIFFRACTION (1.65 Å)