title: Crystal structure of family 4 uracil-DNA glycosylase from Sulfolobus tokodaii and a function of tyrosine 170 in DNA binding.
abstract: 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.
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan. Electronic address: akawai@ph.sojo-u.ac.jp.
authors: Akito
authors: A
authors: Kawai
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
authors: Shigesada
authors: S
authors: Higuchi
authors: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai-iino, Iwaki 970-8551, Japan.
authors: Masaru
authors: M
authors: Tsunoda
authors: School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Kazuo T
authors: KT
authors: Nakamura
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors: Yuriko
authors: Y
authors: Yamagata
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
authors: Shuichi
authors: S
authors: Miyamoto
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016944:Sulfolobus / Q000201:enzymology*; D014443:Tyrosine / Q000378:metabolism*; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D014443:Tyrosine; D014498:Uracil; D004247:DNA; D051981:Uracil-DNA Glycosidase
keywords: Crystal structure; Leucine-intercalation loop; Sulfolobus tokodaii; Uracil–DNA glycosylase