6ER5

X-ray structure of Trypanothione Reductase from Leishmania infantum in complex with 2-(diethylamino)ethyl 4-((3-(4-nitrophenyl)-3-oxopropyl)amino)benzoate

6ER5 の概要

• エントリーDOI: 10.2210/pdb6er5/pdb
• 分子名称: Trypanothione reductase, FLAVIN-ADENINE DINUCLEOTIDE, 2-(diethylamino)ethyl 4-((3-(4-nitrophenyl)-3-oxopropyl)amino)benzoate, ... (4 entities in total)
• 機能のキーワード: trypanothione, trypanothione reductase, leishmania infantum trypanothione reductase inhibitors., oxidoreductase
• 由来する生物種: Leishmania infantum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54162.99

構造登録者

Ilari, A.,Fiorillo, A. (登録日: 2017-10-17, 公開日: 2018-10-31, 最終更新日: 2024-11-20)

主引用文献

Turcano, L.,Torrente, E.,Missineo, A.,Andreini, M.,Gramiccia, M.,Di Muccio, T.,Genovese, I.,Fiorillo, A.,Harper, S.,Bresciani, A.,Colotti, G.,Ilari, A.
Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening.
Plos Negl Trop Dis, 12:e0006969-e0006969, 2018

PubMed Abstract: Trypanothione reductase (TR) is considered to be one of the best targets to find new drugs against Leishmaniasis. This enzyme is fundamental for parasite survival in the host since it reduces trypanothione, a molecule used by the tryparedoxin/tryparedoxin peroxidase system of Leishmania to neutralize hydrogen peroxide produced by host macrophages during infection. In order to identify new lead compounds against Leishmania we developed and validated a new luminescence-based high-throughput screening (HTS) assay that allowed us to screen a library of 120,000 compounds. We identified a novel chemical class of TR inhibitors, able to kill parasites with an IC50 in the low micromolar range. The X-ray crystal structure of TR in complex with a compound from this class (compound 3) allowed the identification of its binding site in a pocket at the entrance of the NADPH binding site. Since the binding site of compound 3 identified by the X-ray structure is unique, and is not present in human homologs such as glutathione reductase (hGR), it represents a new target for drug discovery efforts.

PubMed: 30475811
DOI: 10.1371/journal.pntd.0006969

実験手法

X-RAY DIFFRACTION (3.37 Å)