@article{oai:repo.qst.go.jp:00047746,
 author = {玉田, 太郎 and Waz, Shaimaa(熊本大学大学院薬学教育部) and 中村, 照也(熊本大学大学院薬学教育部) and 平田, 啓介(熊本大学大学院薬学教育部) and 古賀-小川, 由香里(日本医療科学大学) and 池鯉鮒, 麻美(熊本大学大学院薬学教育部) and 有森, 貴夫(大阪大学蛋白質研究所) and 池水, 信二(熊本大学大学院薬学教育部) and 中別府, 雄作(九州大学生体防御医学研究所) and 山縣, ゆり子(熊本大学大学院薬学教育部) and 玉田 太郎},
 issue = {7},
 journal = {The Journal of Biological Chemistry},
 month = {Feb},
 note = {The human MutT homolog 1 (hMTH1, human NUDT1) hydrolyzes oxidatively
damaged nucleoside triphosphates and is the main enzyme responsible for nucleotide
sanitization. Here, we determined crystal structures of hMTH1 in complex with 8-oxo-dGTP or 2-oxo-dATP at neutral pH. These structures showed that the base moieties of two substrates are located on the similar but not the same position in the substrate-binding pocket and adopt a different hydrogen-bonding pattern. Analyses of bond lengths with high-resolution X-ray data and of the relation between the structure and enzymatic activity revealed that hMTH1 recognizes the different oxidized nucleotides via an exchange of the protonation state at two neighboring aspartate residues in its substrate-binding pocket. This mechanism of broad substrate recognition by enzymes has not been reported previously and may have relevance for anticancer drug development strategies targeting hMTH1.},
 pages = {2785--2794},
 title = {Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity},
 volume = {292},
 year = {2017}
}