Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue

被引:127
作者
Färber, PM
Arscott, LD
Williams, CH
Becker, K
Schirmer, RH
机构
[1] Heidelberg Univ, Zentrum Biochem, D-69120 Heidelberg, Germany
[2] Univ Michigan, Dept Vet Affairs Med Ctr, Ann Arbor, MI 48105 USA
[3] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48105 USA
来源
FEBS LETTERS | 1998年 / 422卷 / 03期
关键词
malaria; drug target; disulfide reductase; flavoenzyme; phenothiazine; tryptophan fluorescence;
D O I
10.1016/S0014-5793(98)00031-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页码:311 / 314
页数:4
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