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Molecular basis of dihydrouridine formation on tRNA

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Title: Molecular basis of dihydrouridine formation on tRNA
Authors: Yu, Futao Browse this author
Tanaka, Yoshikazu Browse this author →KAKEN DB
Yamashita, Keitaro Browse this author
Suzuki, Takeo Browse this author
Nakamura, Akiyoshi Browse this author
Hirano, Nagisa Browse this author
Suzuki, Tsutomu Browse this author
Yao, Min Browse this author →KAKEN DB
Tanaka, Isao Browse this author →KAKEN DB
Keywords: protein-tRNA complex
RNA modification
substrate recognition
X-ray crystallography
Issue Date: 6-Dec-2011
Publisher: National Academy of Sciences
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 108
Issue: 49
Start Page: 19593
End Page: 19598
Publisher DOI: 10.1073/pnas.1112352108
Abstract: Dihydrouridine (D) is a highly conserved modified base found in tRNAs from all domains of life. Dihydrouridine synthase (Dus) catalyzes the D formation of tRNA through reduction of uracil base with flavin mononucleotide (FMN) as a cofactor. Here, we report the crystal structures of Thermus thermophilus Dus (TthDus), which is responsible for D formation at positions 20 and 20a, in complex with tRNA and with a short fragment of tRNA (D-loop). Dus interacts extensively with the D-arm and recognizes the elbow region composed of the kissing loop interaction between T- and D-loops in tRNA, pulling U20 into the catalytic center for reduction. Although distortion of the D-loop structure was observed upon binding of Dus to tRNA, the canonical D-loop/T-loop interaction was maintained. These results were consistent with the observation that Dus preferentially recognizes modified rather than unmodified tRNAs, indicating that Dus introduces D20 by monitoring the complete L-shaped structure of tRNAs. In the active site, U20 is stacked on the isoalloxazine ring of FMN, and C5 of the U20 uracil ring is covalently cross-linked to the thiol group of Cys93, implying a catalytic mechanism of D20 formation. In addition, the involvement of a cofactor molecule in uracil ring recognition was proposed. Based on a series of mutation analyses, we propose a molecular basis of tRNA recognition and D formation catalyzed by Dus.
Type: article (author version)
Appears in Collections:創成研究機構 (Creative Research Institution) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 田中 良和

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