3AL6

Crystal structure of Human TYW5

3AL6 の概要

• エントリーDOI: 10.2210/pdb3al6/pdb
• 関連するPDBエントリー: 3AL5
• 分子名称: JmjC domain-containing protein C2orf60, NICKEL (II) ION, 2-OXOGLUTARIC ACID (3 entities in total)
• 機能のキーワード: trna modification enzyme, unknown function
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 157157.53

構造登録者

Kato, M.,Araiso, Y.,Ishitani, R.,Nureki, O. (登録日: 2010-07-26, 公開日: 2010-12-01, 最終更新日: 2024-03-13)

主引用文献

Kato, M.,Araiso, Y.,Noma, A.,Nagao, A.,Suzuki, T.,Ishitani, R.,Nureki, O.
Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification.
Nucleic Acids Res., 39:1576-1585, 2011

PubMed Abstract: Wybutosine (yW) is a hypermodified nucleoside found in position 37 of tRNA(Phe), and is essential for correct phenylalanine codon translation. yW derivatives widely exist in eukaryotes and archaea, and their chemical structures have many species-specific variations. Among them, its hydroxylated derivative, hydroxywybutosine (OHyW), is found in eukaryotes including human, but the modification mechanism remains unknown. Recently, we identified a novel Jumonji C (JmjC)-domain-containing protein, TYW5 (tRNA yW-synthesizing enzyme 5), which forms the OHyW nucleoside by carbon hydroxylation, using Fe(II) ion and 2-oxoglutarate (2-OG) as cofactors. In this work, we present the crystal structures of human TYW5 (hTYW5) in the free and complex forms with 2-OG and Ni(II) ion at 2.5 and 2.8 Å resolutions, respectively. The structure revealed that the catalytic domain consists of a β-jellyroll fold, a hallmark of the JmjC domains and other Fe(II)/2-OG oxygenases. hTYW5 forms a homodimer through C-terminal helix bundle formation, thereby presenting a large, positively charged patch involved in tRNA binding. A comparison with the structures of other JmjC-domain-containing proteins suggested a mechanism for substrate nucleotide recognition. Functional analyses of structure-based mutants revealed the essential Arg residues participating in tRNA recognition by TYW5. These findings extend the repertoire of the tRNA modification enzyme into the Fe(II)/2-OG oxygenase superfamily.

PubMed: 20972222
DOI: 10.1093/nar/gkq919

実験手法

X-RAY DIFFRACTION (2.8 Å)