7YLZ

Unliganded form of hydroxyamidotransferase TsnB9

7YLZ の概要

• エントリーDOI: 10.2210/pdb7ylz/pdb
• 分子名称: hydroxyamidotransferase, SULFATE ION (3 entities in total)
• 機能のキーワード: trichostatin a, biosynthesis, transferase, ligase
• 由来する生物種: Streptomyces sp. RM72
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 141797.57

構造登録者

Nagata, R.,Nishiyama, M.,Kuzuyama, T. (登録日: 2022-07-27, 公開日: 2023-05-31, 最終更新日: 2024-04-03)

主引用文献

Nagata, R.,Nishiyama, M.,Kuzuyama, T.
Substrate Recognition Mechanism of a Trichostatin A-Forming Hydroxyamidotransferase.
Biochemistry, 62:1833-1837, 2023

PubMed Abstract: The hydroxyamidotransferase TsnB9 catalyzes hydroxylamine transfer from l-glutamic acid γ-monohydroxamate to the carboxyl group of trichostatic acid to produce the terminal hydroxamic acid group of trichostatin A, which is a potent inhibitor of histone deacetylase (HDAC). The reaction catalyzed by TsnB9 is similar to that catalyzed by glutamine-dependent asparagine synthetase, but the trichostatic acid recognition mechanism remains unclear. Here, we determine the crystal structure of TsnB9 composed of the N-terminal glutaminase domain and the C-terminal synthetase domain. Two consecutive phenylalanine residues, which are not found in glutamine-dependent asparagine synthetase, in the N-terminal glutaminase domain structurally form the bottom of the hydrophobic pocket in the C-terminal synthetase domain. Mutational and computational analyses of TsnB9 suggest five aromatic residues, including the two consecutive phenylalanine residues, in the hydrophobic pocket are important for the recognition of the dimethylaniline moiety of trichostatic acid. These insights lead us to the discovery of hydroxyamidotransferase to produce terminal hydroxamic acid group-containing HDAC inhibitors different from trichostatin A.

PubMed: 37167424
DOI: 10.1021/acs.biochem.3c00025

実験手法

X-RAY DIFFRACTION (2.72 Å)