2W0H

X ray structure of Leishmania infantum Trypanothione reductase in complex with antimony and NADPH

2W0H の概要

• エントリーDOI: 10.2210/pdb2w0h/pdb
• 関連するPDBエントリー: 2JK6
• 分子名称: TRYPANOTHIONE REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE, ANTIMONY (III) ION, ... (6 entities in total)
• 機能のキーワード: fad, leishamnia, antimonials, flavoprotein, reduced nadph, oxidoreductase, redox-active center, trypanothione metabolism
• 由来する生物種: LEISHMANIA INFANTUM
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114012.68

構造登録者

Baiocco, P.,Colotti, G.,Franceschini, S.,Ilari, A. (登録日: 2008-08-18, 公開日: 2009-04-28, 最終更新日: 2023-12-13)

主引用文献

Baiocco, P.,Colotti, G.,Franceschini, S.,Ilari, A.
Molecular Basis of Antimony Treatment in Leishmaniasis.
J.Med.Chem., 52:2603-, 2009

PubMed Abstract: Leishmaniasis is a disease that affects 2 million people and kills 70000 persons every year. It is caused by Leishmania species, which are human protozoan parasites of the trypanosomatidae family. Trypanosomatidae differ from the other eukaryotes in their specific redox metabolism because the glutathione/glutathione reductase system is replaced by the unique trypanothione/trypanothione reductase system. The current treatment of leishmaniasis relies mainly on antimonial drugs. The crystal structures of oxidized trypanothione reductase (TR) from Leishmania infantum and of the complex of reduced TR with NADPH and Sb(III), reported in this paper, disclose for the first time the molecular mechanism of action of antimonial drugs against the parasite. Sb(III), which is coordinated by the two redox-active catalytic cysteine residues (Cys52 and Cys57), one threonine residue (Thr335), and His461' of the 2-fold symmetry related subunit in the dimer, strongly inhibits TR activity. Because TR is essential for the parasite survival and virulence and it is absent in mammalian cells, these findings provide insights toward the design of new more affordable and less toxic drugs against Leishmaniasis.

PubMed: 19317451
DOI: 10.1021/JM900185Q

実験手法

X-RAY DIFFRACTION (3 Å)