Mukhopadhyay Rita, Rosen Barry P
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):745-8. doi: 10.1289/ehp.02110s5745.
The ubiquity of arsenic in the environment has led to the evolution of enzymes for arsenic detoxification. An initial step in arsenic metabolism is the enzymatic reduction of arsenate [As(V)] to arsenite [As(III)]. At least three families of arsenate reductase enzymes have arisen, apparently by convergent evolution. The properties of two of these are described here. The first is the prokaryotic ArsC arsenate reductase of Escherichia coli. The second, Acr2p of Saccharomyces cerevisiae, is the only identified eukaryotic arsenate reductase. Although unrelated to each other, both enzymes receive their reducing equivalents from glutaredoxin and reduced glutathione. The structure of the bacterial ArsC has been solved at 1.65 A. As predicted from its biochemical properties, ArsC structures with covalent enzyme-arsenic intermediates that include either As(V) or As(III) were observed. The yeast Acr2p has an active site motif HC(X)(5)R that is conserved in protein phosphotyrosine phosphatases and rhodanases, suggesting that these three groups of enzymes may have evolved from an ancestral oxyanion-binding protein.
环境中砷的普遍存在导致了用于砷解毒的酶的进化。砷代谢的第一步是将砷酸盐[As(V)]酶促还原为亚砷酸盐[As(III)]。至少出现了三个砷酸盐还原酶家族，显然是通过趋同进化产生的。这里描述了其中两个家族的特性。第一个是大肠杆菌的原核ArsC砷酸盐还原酶。第二个是酿酒酵母的Acr2p，它是唯一已鉴定的真核砷酸盐还原酶。尽管这两种酶彼此不相关，但它们都从谷氧还蛋白和还原型谷胱甘肽获得还原当量。细菌ArsC的结构已在1.65埃的分辨率下解析出来。正如从其生化特性所预测的那样，观察到了具有共价酶-砷中间体（包括As(V)或As(III)）的ArsC结构。酵母Acr2p具有一个活性位点基序HC(X)(5)R，该基序在蛋白质酪氨酸磷酸酶和硫氰酸酶中保守，这表明这三组酶可能是从一个祖先的氧阴离子结合蛋白进化而来的。
