7XH2

Dihydrofolate Reductase-like Protein SacH in safracin biosynthesis

7XH2 の概要

• エントリーDOI: 10.2210/pdb7xh2/pdb
• 分子名称: Uncharacterized protein sfcH, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: reductase, safracin biosynthesis, self-resistance., oxidoreductase
• 由来する生物種: Pseudomonas fluorescens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22764.26

構造登録者

Ma, X.,Shao, N.,Ma, M.,Tang, G. (登録日: 2022-04-07, 公開日: 2023-02-08, 最終更新日: 2023-11-29)

主引用文献

Shao, N.,Ma, X.,Zhang, Y.Y.,Yang, D.,Ma, M.,Tang, G.L.
Dihydrofolate reductase-like protein inactivates hemiaminal pharmacophore for self-resistance in safracin biosynthesis.
Acta Pharm Sin B, 13:1318-1325, 2023

PubMed Abstract: Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH-NADPH-SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore. These findings expand the functions of DHFR family proteins, reveal that the common reaction can be catalyzed by distinct family of enzymes, and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.

PubMed: 36970210
DOI: 10.1016/j.apsb.2022.10.005

実験手法

X-RAY DIFFRACTION (2.8 Å)