Kawai Akito, Higuchi Shigesada, Tsunoda Masaru, Nakamura Kazuo T, Yamagata Yuriko, Miyamoto Shuichi
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
FEBS Lett. 2015 Sep 14;589(19 Pt B):2675-82. doi: 10.1016/j.febslet.2015.08.019. Epub 2015 Aug 28.
Uracil-DNA glycosylases (UDGs) excise uracil from DNA by catalyzing the N-glycosidic bond hydrolysis. Here we report the first crystal structures of an archaeal UDG (stoUDG). Compared with other UDGs, stoUDG has a different structure of the leucine-intercalation loop, which is important for DNA binding. The stoUDG-DNA complex model indicated that Leu169, Tyr170, and Asn171 in the loop are involved in DNA intercalation. Mutational analysis showed that Tyr170 is critical for substrate DNA recognition. These results indicate that Tyr170 occupies the intercalation site formed after the structural change of the leucine-intercalation loop required for the catalysis.
尿嘧啶-DNA糖基化酶（UDGs）通过催化N-糖苷键水解从DNA中切除尿嘧啶。在此，我们报道了古细菌UDG（stoUDG）的首个晶体结构。与其他UDGs相比，stoUDG的亮氨酸插入环结构不同，该环对DNA结合很重要。stoUDG-DNA复合物模型表明，环中的Leu169、Tyr170和Asn171参与DNA插入。突变分析表明，Tyr170对底物DNA识别至关重要。这些结果表明，Tyr170占据了催化所需的亮氨酸插入环结构变化后形成的插入位点。
