Structural basis for the retroreduction of inactivated peroxiredoxins by human sulfiredoxin
Structural basis for the retroreduction of inactivated peroxiredoxins by human sulfiredoxin
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DOI：
10.1021/bi050131i
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发表时间：
2005-06-21
期刊：
影响因子：
2.9
通讯作者：
Lowther, WT
中科院分区：
文献类型：
--
作者：
Jönsson, TJ;Murray, MS;Lowther, WT
硫氧还蛋白(SRX)修复过氧化氢介导的细胞信号中典型的双半胱氨酸过氧化还蛋白(PRX)的失活形式。SRX还原Prx活性中心内的半胱氨酸亚磺酸部分涉及到新的硫化学以及ATP和Mg2+的使用。人SRx(HSrx)的1.65埃晶体结构显示了一个新的蛋白质折叠和一个独特的核苷酸结合基序，该基序在α-螺旋的N端含有Gly98-Cys99-His100-Arg101序列。对反应产物的高效液相色谱分析证实，ATP的裂解位置在和伽马-磷酸之间。Cys99和ATP的伽马磷酸在2.0埃ADP产物复杂结构的活性部位建模，毗邻包含额外保守残基的大型表面凹陷。这些特征以及对Prx结构进行重大重塑的必要性表明，hSrx与典型的Two-Cys Prx之间的相互作用是特定的。此外，hSrx活性中心表面的凹面形状似乎非常适合与环形PRX分解器的凸面相互作用。
Sufiredoxins (Srx) repair the inactivated forms of typical two-Cys peroxiredoxins (Prx) implicated in hydrogen peroxide-mediated cell signaling. The reduction of the cysteine sulfinic acid moiety within the active site of the Prx by Srx involves novel sulfur chemistry and the use of ATP and Mg2+. The 1.65 angstrom crystal structure of human Srx (hSrx) exhibits a new protein fold and a unique nucleotide binding motif containing the Gly98-Cys99-His100-Arg101 sequence at the N-terminus of an alpha-helix. HPLC analysis of the reaction products has confirmed that the site of ATP cleavage is between the and gamma-phosphate groups. Cys99 and the gamma-phosphate of ATP, modeled within the active site of the 2.0 angstrom ADP product complex structure, are adjacent to large surface depressions containing additional conserved residues. These features and the necessity for significant remodeling of the Prx structure suggest that the interactions between hSrx and typical two-Cys Prxs are specific. Moreover, the concave shape of the hSrx active site surface appears to be ideally suited to interacting with the convex surface of the toroidal Prx decamer.