Crystal structure of AhpE from Mycobacterium tuberculosis, a 1-Cys peroxiredoxin
Crystal structure of AhpE from Mycobacterium tuberculosis, a 1-Cys peroxiredoxin
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DOI：
10.1016/j.jmb.2004.12.046
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发表时间：
2005-03-04
影响因子：
5.6
通讯作者：
Baker, EN
中科院分区：
文献类型：
--
作者：
Li, S;Peterson, NA;Baker, EN
所有的生命系统都需要保护以免受活性氧的破坏性影响。结核分枝杆菌的基因组编码许多过氧化物酶，这些过氧化物酶被认为对有机和无机过氧化物具有活性，并且可能在该生物体在巨噬细胞的吞噬体内存活的能力中发挥关键作用。M中的开放阅读帧Rv 2238 c。结核分枝杆菌编码153个残基的蛋白AhpE，其是1-Cys过氧化物氧还蛋白（Prx）家族的过氧化物酶。在1.87埃分辨率下测定的AhpE的晶体结构（R-cryst=0.179，R-free=0.210）揭示了具有硫氧还蛋白折叠的紧凑的单结构域蛋白。AhpE形成二聚体和八聚体;紧密缔合的二聚体和环状八聚体，由晶体学4重对称产生。在这种天然结构中，活性位点Cys 45处于其氧化的次磺酸（S-O-H）状态。在溴化钠中浸泡并在1.90埃分辨率下精制后获得的AhpE的第二种晶体形式（R-cryst=0.242，R-free=0.286）显示了还原的结构。在这种结构中，外部环中的构象变化，在不对称单元中的四个分子中的两个中，允许Arg 116稳定Cys 45硫醇盐离子，并伴随关闭表面通道。该通道被确定为生理还原剂的可能结合位点，并且推测构象变化对AhpE的反应循环是重要的。(C)2004爱思唯尔有限公司保留所有权利。
All living systems require protection against the damaging effects of reactive oxygen species. The genome of Mycobacterium tuberculosis, the cause of TB, encodes a number of peroxidases that are thought to be active against organic and inorganic peroxides, and are likely to play a key role in the ability of this organism to survive within the phagosomes of macrophages. The open reading frame Rv2238c in M. tuberculosis encodes a 153-residue protein AhpE, which is a peroxidase of the 1-Cys peroxiredoxin (Prx) family. The crystal structure of AhpE, determined at 1.87 Angstrom resolution (R-cryst=0.179, R-free=0.210), reveals a compact single-domain protein with a thioredoxin fold. AhpE forms both dimers and octamers; a tightly-associated dimer and a ring-like octamer, generated by crystallographic 4-fold symmetry. In this native structure, the active site Cys45 is in its oxidized, sulfenic acid (S-O-H) state. A second crystal form of AhpE, obtained after soaking in sodium bromide and refined at 1.90 Angstrom resolution (R-cryst=0.242, R-free=0.286), reveals the reduced structure. In this structure, a conformational change in an external loop, in two of the four molecules in the asymmetric unit, allows Arg116 to stabilise the Cys45 thiolate ion, and concomitantly closes a surface channel. This channel is identified as the likely binding site for a physiological reductant, and the conformational change is inferred to be important for the reaction cycle of AhpE. (C) 2004 Elsevier Ltd. All rights reserved.