Structure and mechanism of peptide methionine sulfoxide reductase, an "anti-oxidation" enzyme
Structure and mechanism of peptide methionine sulfoxide reductase, an "anti-oxidation" enzyme
复制标题
DOI：
10.1021/bi0020269
复制
发表时间：
2000-11-07
期刊：
影响因子：
2.9
通讯作者：
Matthews, BW
中科院分区：
文献类型：
--
作者：
Lowther, WT;Brot, N;Matthews, BW
肽蛋氨酸亚砜还原酶 (MsrA) 可逆转游离蛋氨酸和蛋白质内蛋氨酸的氧化损伤。因此，它有助于保护宿主生物体免受可能导致细胞死亡的随机损伤。牛 MsrA 的结构已通过两种不同的修饰确定，这两种修饰都提供了对该蛋白质生物学的不同见解。活性位点附近有三个半胱氨酸残基。富含甘氨酸的 C 末端尾部的构象变化似乎使所有三种硫醇聚集在一起并参与催化。该结构支持独特的硫醇-二硫化物交换机制，该机制依赖于作为亲核试剂的必需半胱氨酸以及与亚砜部分的氧原子相互作用的额外保守残基。
Peptide methionine sulfoxide reductase (MsrA) reverses oxidative damage to both free methionine and methionine within proteins. As such, it helps protect the host organism against stochastic damage that can contribute to cell death. The structure of bovine MsrA has been determined in two different modifications, both of which provide different insights into the biology of the protein. There are three cysteine residues located in the vicinity of the active site. Conformational changes in a glycine-rich C-terminal tail appear to allow all three thiols to come together and to participate in catalysis. The structures support a unique, thiol-disulfide exchange mechanism that relies upon an essential cysteine as a nucleophile and additional conserved residues that interact with the oxygen atom of the sulfoxide moiety.