Cai Jian-Ping, Ishibashi Toru, Takagi Yasumitsu, Hayakawa Hiroshi, Sekiguchi Mutsuo
Department of Biology and Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan.
Biochem Biophys Res Commun. 2003 Jun 13;305(4):1073-7. doi: 10.1016/s0006-291x(03)00864-7.
MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis, in the nucleotide pool, thereby preventing DNA replication errors. During a search of GenBank EST database, we found a new member of MutT-related protein, MTH2, which possesses the 23-amino acid MutT module. The cloned mouse MTH2 (mMTH2) cDNA was expressed in Escherichia coli mutT(-) cells and the protein was purified. mMTH2 protein hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, with Km of 32 microM. Expression of cDNA for mMTH2 reduced significantly the elevated level of spontaneous mutation frequency of E. coli mutT(-) cells. Thus, MTH2 has a potential to protect the genetic material from the untoward effects of endogenous oxygen radicals. MTH2 could act as an MTH1 redundancy factor.
MutT相关蛋白在核苷酸池中降解8-氧代-7,8-二氢脱氧鸟苷三磷酸（8-氧代-dGTP），这是一种DNA合成的诱变底物，从而防止DNA复制错误。在搜索GenBank EST数据库时，我们发现了MutT相关蛋白的一个新成员MTH2，它具有23个氨基酸的MutT模块。克隆的小鼠MTH2（mMTH2）cDNA在大肠杆菌mutT（-）细胞中表达，并对该蛋白进行了纯化。mMTH2蛋白将8-氧代-dGTP水解为8-氧代-dGMP，Km为32微摩尔。mMTH2 cDNA的表达显著降低了大肠杆菌mutT（-）细胞自发突变频率的升高水平。因此，MTH2有潜力保护遗传物质免受内源性氧自由基的不良影响。MTH2可能作为MTH1的冗余因子发挥作用。
