6AJ5

Crystal structure of ligand-free type DHODH from Eimeria tenella

6AJ5 の概要

• エントリーDOI: 10.2210/pdb6aj5/pdb
• 分子名称: Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID (3 entities in total)
• 機能のキーワード: coccidium, mitochondria, electron transport chain, dihydroorotate dehydrogenase, membrane protein
• 由来する生物種: Eimeria tenella (Coccidian parasite)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 197618.46

構造登録者

Shiba, T.,Inaoka, D.K.,Sato, D.,Hartuti, E.D.,Amalia, E.,Nagahama, M.,Yoshioka, Y.,Matsubayashi, M.,Balogun, E.O.,Tsuji, N.,Kita, K.,Harada, S. (登録日: 2018-08-27, 公開日: 2019-08-28, 最終更新日: 2024-10-23)

主引用文献

Sato, D.,Hartuti, E.D.,Inaoka, D.K.,Sakura, T.,Amalia, E.,Nagahama, M.,Yoshioka, Y.,Tsuji, N.,Nozaki, T.,Kita, K.,Harada, S.,Matsubayashi, M.,Shiba, T.
Structural and Biochemical Features of Eimeria tenella Dihydroorotate Dehydrogenase, a Potential Drug Target.
Genes (Basel), 11:-, 2020

PubMed Abstract: Dihydroorotate dehydrogenase (DHODH) is a mitochondrial monotopic membrane protein that plays an essential role in the pyrimidine de novo biosynthesis and electron transport chain pathways. In , an intracellular apicomplexan parasite that causes the most severe form of chicken coccidiosis, the activity of pyrimidine salvage pathway at the intracellular stage is negligible and it relies on the pyrimidine de novo biosynthesis pathway. Therefore, the enzymes of the de novo pathway are considered potential drug target candidates for the design of compounds with activity against this parasite. Although, DHODHs from (EtDHODH), (PfDHODH), and human (HsDHODH) show distinct sensitivities to classical DHODH inhibitors, in this paper, we identify ferulenol as a potent inhibitor of both EtDHODH and HsDHODH. Additionally, we report the crystal structures of EtDHODH and HsDHODH in the absence and presence of ferulenol. Comparison of these enzymes showed that despite similar overall structures, the EtDHODH has a long insertion in the N-terminal helix region that assumes a disordered configuration. In addition, the crystal structures revealed that the ferulenol binding pocket of EtDHODH is larger than that of HsDHODH. These differences can be explored to accelerate structure-based design of inhibitors specifically targeting EtDHODH.

PubMed: 33297567
DOI: 10.3390/genes11121468

実験手法

X-RAY DIFFRACTION (3.5 Å)