Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue
Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue
复制标题
DOI：
10.1016/s0014-5793(98)00031-3
复制
发表时间：
1998-02-06
期刊：
影响因子：
3.5
通讯作者：
Schirmer, RH
中科院分区：
文献类型：
--
作者：
Färber, PM;Arscott, LD;Schirmer, RH
恶性疟原虫谷胱甘肽还原酶（Plasmodiumfalciparumglutathione reductase，PfGR）已成为治疗热带疟疾的药物靶点。重组PfGR在其酶性质上与真实酶没有区别，周转数为9900 min（-1）。二聚体黄素酶显示氧化还原依赖性吸收光谱;单个色氨酸残基（每57.2 kDa亚基）具有强荧光。PfGR可被治疗浓度的抗疟药亚甲蓝抑制;非竞争性抑制的Ki为6.4 μ M。在高离子强度下也观察到对亚甲蓝的敏感性，因此，通过与人GR类似，可以设想对结晶酶-药物复合物的分析。(C)1998年欧洲生物化学学会联合会。
Plasmodium falciparum glutathione reductase (PfGR) has emerged as a drug target against tropical malaria, Here me report the expression of PfGR in Escherichia coli SG5(DE3) and isolation procedures for this protein. Recombinant PfGR does not differ from the authentic enzyme in its enzymic properties, the turnover number being 9900 min(-1), The dimeric flavoenzyme exhibits redox-dependent absorption spectra; the single tryptophan residue (per 57.2 kDa subunit) is strongly fluorescent. PfGR can be inhibited by the antimalarial drug methylene blue at therapeutic concentrations; the K-i for non-competitive inhibition is 6.4 mu M. The sensitivity to methylene blue is observed also at high ionic strength so that, by analogy to human GR, analysis of crystalline enzyme-drug complexes can be envisaged. (C) 1998 Federation of European Biochemical Societies.