The Structure of Reduced Tryparedoxin Peroxidase Reveals a Decamer and Insight into Reactivity of 2Cys-peroxiredoxins

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• 作者：Alphey ; Magnus S. ; Bond ; Charles S. ; Tetaud ; Emmanuel ; Fairlamb ; Alan H. ; Hunter ; William N.
• 刊名：Journal of Molecular Biology
• 出版年：2000
• 出版时间：July 21, 2000
• 年：2000
• 卷：300
• 期：4
• 页码：903-916
• 全文大小：839 K

文摘

Tryparedoxin peroxidase (TryP) is a recently discovered 2Cys-peroxiredoxin involved in defence against oxidative stress in parasitic trypanosomatids. The crystal structure of recombinant Crithidiafasciculata 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 3.2Å resolution (1Å=0.1nm), 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 super-family. 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.