Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate
Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate
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DOI：
10.1073/pnas.0709822105
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发表时间：
2008-04-29
影响因子：
11.1
通讯作者：
Inoue, Tsuyoshi
中科院分区：
文献类型：
--
作者：
Nakamura, Tsutomu;Yamamoto, Takahiko;Inoue, Tsuyoshi
蛋白质中硫醇基团的氧化是生化过程中的一种常见事件，涉及二硫键的形成和对活性氧物种水平的反应。人们普遍认为半胱氨酸侧链的氧化是由半胱氨酸磺酸(Cys-SOH)的形成引发的。在这里，我们通过展示来自古生菌的过氧化还蛋白(PRx)，来自Aeropyrum pemix K1的硫氧还蛋白过氧化物酶(ApTPx)的结晶学证据，证明了硫醇通过高价硫中间体氧化的机制。Prx的反应是过氧化氢的还原，依赖于氧化还原活性的半胱氨酸侧链。过氧化氢氧化将ApTPx的活性中心过氧半胱氨酸Cys-50转化为半胱氨酸磺酸衍生物，然后进一步氧化为半胱氨酸亚磺酸和磺酸。半胱氨酸磺酸衍生物的晶体结构被细化到1.77埃分辨率，R-Cryst值和R值分别为18.8%和22.0%。精细的结构和量子化学计算表明，磺酸衍生物是一种硫烷，一种高价硫化合物，S-伽马原子与邻近的HIS-42的N-三角洲1原子共价连接。通过过氧化半胱氨酸周围的氢键网络和覆盖活性中心的柔性环的运动以及量子化学计算，揭示了反应机理。这项研究为高价硫化合物在生化过程中占有重要地位提供了证据。
The oxidation of thiol groups in proteins is a common event in biochemical processes involving disulfide bond formation and in response to an increased level of reactive oxygen species. It has been widely accepted that the oxidation of a cysteine side chain is initiated by the formation of cysteine sulfenic acid (Cys-SOH). Here, we demonstrate a mechanism of thiol oxidation through a hyper-valent sulfur intermediate by presenting crystallographic evidence from an archaeal peroxilredoxin (Prx), the thioredoxin peroxidase from Aeropyrum pemix K1 (ApTPx). The reaction of Prx, which is the reduction of a peroxide, depends on the redox active cysteine side chains. Oxidation by hydrogen peroxide converted the active site peroxidatic Cys-50 of ApTPx to a cysteine sulfenic acid derivative, followed by further oxidation to cysteine sulfinic and sulfonic acids. The crystal structure of the cysteine sulfenic acid derivative was refined to 1.77 angstrom resolution with R-cryst and R-free values of 18.8% and 22.0%, respectively. The refined structure, together with quantum chemical calculations, revealed that the sulfenic acid derivative is a type of sulfurane, a hypervalent sulfur compound, and that the S-gamma atom is covalently linked to the N-delta 1 atom of the neighboring His-42. The reaction mechanism is revealed by the hydrogen bond network around the peroxidatic cysteine and the motion of the flexible loop covering the active site and by quantum chemical calculations. This study provides evidence that a hypervalent sulfur compound occupies an important position in biochemical processes.