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首页> 外文期刊>Acta crystallographica. Section D, Biological crystallography. >A di-sulfide-bond cascade mechanism for arsenic(III) S-adenosylme-thionine methyltransferase
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A di-sulfide-bond cascade mechanism for arsenic(III) S-adenosylme-thionine methyltransferase

机译:di-sulfide-bond级联机制甲基转移酶

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Methylation of the toxic metalloid arsenic is widespread in nature. Members of every kingdom have arsenic(III) S-adenosylmethionine (SAM) methyltransferase enzymes, which are termed ArsM in microbes and AS3MT in animals, including humans. Trivalent arsenic(III) is methylated up to three times to form methylarsenite [MAs(III)], dimethylarsenite [DMAs(III)] and the volatile trimethylarsine [TMAs(III)]. In microbes, arsenic methylation is a detoxification process. In humans, MAs(III) and DMAs(III) are more toxic and carcinogenic than either inorganic arsenate or arsenite. Here, new crystal structures are reported of ArsM from the thermophilic eukaryotic alga Cyanidioschyzon sp. 5508 (CmArsM) with the bound aromatic arsenicals phenylarsenite [PhAs(III)] at 1.80?? resolution and reduced roxarsone [Rox(III)] at 2.25?? resolution. These organoarsenicals are bound to two of four conserved cysteine residues: Cys174 and Cys224. The electron density extends the structure to include a newly identified conserved cysteine residue, Cys44, which is disulfide-bonded to the fourth conserved cysteine residue, Cys72. A second disulfide bond between Cys72 and Cys174 had been observed previously in a structure with bound SAM. The loop containing Cys44 and Cys72 shifts by nearly 6.5?? in the arsenic(III)-bound structures compared with the SAM-bound structure, which suggests that this movement leads to formation of the Cys72–Cys174 disulfide bond. A model is proposed for the catalytic mechanism of arsenic(III) SAM methyltransferases in which a disulfide-bond cascade maintains the products in the trivalent state
机译:有毒金属砷甲基化广泛的在自然界中。砷(III) S-adenosylmethionine (SAM)甲基转移酶的酶,称为ArsM在微生物和AS3MT动物,包括人类。三次形成methylarsenite (MAs (III)),对于dimethylarsenite [(III)]和波动trimethylarsine (tma (III)]。甲基化是一个排毒的过程。对于人类,MAs (III)和(III)更有毒比无机砷酸或致癌亚砷酸盐。高温真核ArsM的报道海藻Cyanidioschyzon sp 5508 (CmArsM)绑定芳香phenylarsenite偏方(pha (III)]为1.80 ? ?罗沙胂(火箭(III)) 2.25 ? ?organoarsenicals注定要两个四保守的半胱氨酸残基:Cys174 Cys224。电子密度扩展结构包括一个新发现的守恒的半胱氨酸残留物,Cys44 disulfide-bonded到第四守恒的半胱氨酸残基,Cys72。第二个二硫键Cys72和Cys174之间之前已经被观察到的结构山姆。转变了近6.5 ? ?结构与SAM-bound结构相比,这表明这个运动导致Cys72-Cys174的形成二硫键。模型提出了催化机理砷(III)山姆的甲基转移酶二硫键级联维护的产品三价态

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