The structure of reduced tryparedoxin peroxidase reveals a decamer and insight into reactivity of 2Cys-peroxiredoxins

被引:137
作者
Alphey, MS
Bond, CS
Tetaud, E
Fairlamb, AH
Hunter, WN [1 ]
机构
[1] Univ Dundee, Wellcome Trust Bioctr, Dept Biochem, Dundee DD1 5EH, Scotland
[2] Univ Bordeaux 2, Mol Parasitol Lab, CNRS, UPRESA 5016, F-33076 Bordeaux, France
关键词
Crithidia fasciculata; peroxidase; tryparedoxin; trypanosomatids; X-ray structure;
D O I
10.1006/jmbi.2000.3881
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
Tryparedoxin peroxidase (TryP) is a recently discovered 2Cys-peroxiredoxin involved in defence against oxidative stress in parasitic trypanosomatids. The crystal structure of recombinant Crithidia fasciculata TryP, in the reduced state, has been determined using multi-wavelength anomalous dispersion methods applied to a selenomethionyl derivative. The model comprises a decamer with 52 symmetry, ten chloride ions with 23 water molecules and has been refined, using data to 3.2 Angstrom resolution (1 Angstrom = 0.1 nm), to an R-factor and R-free of 27.3 and 28.6 %, respectively. Secondary structure topology places TryP along with tryparedoxin and glutathione peroxidase in a distinct subgroup of the thioredoxin superfamily. The molecular details at the active site support ideas about the enzyme mechanism and comparisons with an oxidised 2Cys-peroxiredoxin reveal structural alterations induced by the change in oxidation state. These include a difference in quaternary structure from dimer (oxidised form) to decamer (reduced form). The 2Cys-peroxiredoxin assembly may prevent indiscriminate oligomerisation, localise ten peroxidase active sites and contribute to both the specificity of reduction by the redox partner tryparedoxin and attraction of peroxides into the active site. (C) 2000 Academic Press.
引用
收藏
页码:903 / 916
页数:14
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