Improved Catenated Structures of Bovine Peroxiredoxin III F190L Reveal Details of Ring-Ring Interactions and a Novel Conformational State.

Improved Catenated Structures of Bovine Peroxiredoxin III F190L Reveal Details of Ring-Ring Interactions and a Novel Conformational State.
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DOI:
10.1371/journal.pone.0123303
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Lindsay JG
Lindsay JG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao Z;McGow DP;Shepherd C;Lindsay JG

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线粒体2-cys过氧化物还氧蛋白III (PrxIII)在抗氧化防御中将局部生成的H2O2还原为H2O的过程中起着关键作用。PrxIII的c端α-螺旋上出现了与某些细菌和寄生虫相似的Phe to Leu (F190L)突变,增强了PrxIII的抗高氧化能力,但对过氧化物酶活性无明显影响。本文报道了牛PrxIII F190L在2.4 Å和2.2 Å的氧化和还原晶体结构。这两种结构都以双环链链的形式存在,它们的十二聚体环彼此倾斜成550度,类似于先前报道的PrxIII C168S。新的高分辨率结构揭示了稳定环面间接触的复杂氢键网络的细节。此外,通常与催化cys (Cp, cys 47)相互作用的关键保守残基Arg123以独特的构象从Cp延伸而出,而支撑活性位点几何结构的特征Arg-Glu-Arg网络也显示出独特的排列,这是以前未观察到的。这种新颖的活性位点组织可能为氧化态和还原态之间发生的大规模构象变化的动力学提供新的见解。
Mitochondrial 2-cys peroxiredoxin III (PrxIII) is a key player in antioxidant defence reducing locally-generated H2O2 to H2O. A Phe to Leu (F190L) mutation in the C-terminal α-helix of PrxIII, mimicking that found in some bacteria and parasites, increases its resistance to hyperoxidation but has no obvious influence on peroxidase activity. Here we report on the oxidized and reduced crystal structures of bovine PrxIII F190L at 2.4 Å and 2.2 Å, respectively. Both structures exist as two-ring catenanes with their dodecameric rings inclined at 55o to each other, similar to that previously reported for PrxIII C168S. The new higher-resolution structures reveal details of the complex network of H-bonds stabilising the inter-toroid contacts. In addition, Arg123, the key conserved residue, that normally interacts with the catalytic cys (Cp, cys 47) is found in a distinct conformation extending away from the Cp while the characteristic Arg-Glu-Arg network, underpinning the active-site geometry also displays a distinctive arrangement, not observed previously. This novel active-site organisation may provide new insights into the dynamics of the large-scale conformational changes occurring between oxidized and reduced states.
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