4EF8

Crystal structure of dihydroorotate dehydrogenase from Leishmania major in complex with Phenyl isothiocyanate

4EF8 の概要

• エントリーDOI: 10.2210/pdb4ef8/pdb
• 関連するPDBエントリー: 4EF9
• 分子名称: Dihydroorotate dehydrogenase, FLAVIN MONONUCLEOTIDE, N-phenylthioformamide, ... (6 entities in total)
• 機能のキーワード: leishmania major, dihydroorotate dehydrogenase, phenyl isothiocyanate, pyrd, oxidoreductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Leishmania major
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78066.65

構造登録者

Pinheiro, M.P.,Emery, F.S.,Nonato, M.C. (登録日: 2012-03-29, 公開日: 2012-12-12, 最終更新日: 2024-10-09)

主引用文献

Pinheiro, M.P.,Emery, F.S.,Nonato, M.C.
Target sites for the design of anti-trypanosomatid drugs based on the structure of dihydroorotate dehydrogenase.
Curr.Pharm.Des., 19:2615-2627, 2013

PubMed Abstract: Trypanosomatids consist of a large group of flagellated parasitic protozoa, including parasites from the genera Leishmania and Trypanosoma, responsible for causing infections in millions of humans worldwide and for which currently no appropriate therapy is available. The significance of pyrimidines in cellular metabolism makes their de novo and salvage pathways ideal druggable targets for pharmacological intervention and open an opportunity for pharmaceutical innovation. In the current review, we discuss the merits in targeting the enzyme dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes the fourth and only redox step in pyrimidine de novo biosynthesis, as a strategy for the development of efficient therapeutic strategies for trypanosomatid-related diseases.We also describe the advances and perspectives from the structural biology point of view in order to unravel the structure-function relationship of trypanosomatid DHODHs, and to identify and validate target sites for drug development.

PubMed: 23116399

実験手法

X-RAY DIFFRACTION (1.56 Å)