2WBA

Properties of Trypanothione Reductase From T. brucei

「2VE2」から置き換えられました

2WBA の概要

• エントリーDOI: 10.2210/pdb2wba/pdb
• 分子名称: TRYPANOTHIONE REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: redox-active center, flavoprotein, trypnothione metabolism oxidoreductase, oxidoreductase
• 由来する生物種: TRYPANOSOMA BRUCEI BRUCEI
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 110616.42

構造登録者

Jones, D.,Ariza, A.,Chow, W.H.A.,Oza, S.L.,Fairlamb, A.H. (登録日: 2009-02-24, 公開日: 2009-11-24, 最終更新日: 2024-11-20)

主引用文献

Jones, D.,Ariza, A.,Chow, W.H.A.,Oza, S.L.,Fairlamb, A.H.
Comparative Structural, Kinetic and Inhibitor Studies of Trypanosoma Brucei Trypanothione Reductase with T. Cruzi.
Mol.Biochem.Parasitol., 169:12-, 2010

PubMed Abstract: As part of a drug discovery programme to discover new treatments for human African trypanosomiasis, recombinant trypanothione reductase from Trypanosoma brucei has been expressed, purified and characterized. The crystal structure was solved by molecular replacement to a resolution of 2.3A and found to be nearly identical to the T. cruzi enzyme (root mean square deviation 0.6A over 482 Calpha atoms). Kinetically, the K(m) for trypanothione disulphide for the T. brucei enzyme was 4.4-fold lower than for T. cruzi measured by either direct (NADPH oxidation) or DTNB-coupled assay. The K(m) for NADPH for the T. brucei enzyme was found to be 0.77microM using an NADPH-regenerating system coupled to reduction of DTNB. Both enzymes were assayed for inhibition at their respective S=K(m) values for trypanothione disulphide using a range of chemotypes, including CNS-active drugs such as clomipramine, trifluoperazine, thioridazine and citalopram. The relative IC(50) values for the two enzymes were found to vary by no more than 3-fold. Thus trypanothione reductases from these species are highly similar in all aspects, indicating that they may be used interchangeably for structure-based inhibitor design and high-throughput screening.

PubMed: 19747949
DOI: 10.1016/J.MOLBIOPARA.2009.09.002

実験手法

X-RAY DIFFRACTION (2.3 Å)