7ULC

Crystal structure of queuine salvage enzyme DUF2419 mutant D231N, in complex with queuosine-5'-monophosphate

7ULC の概要

• エントリーDOI: 10.2210/pdb7ulc/pdb
• 関連するPDBエントリー: 7U07
• 分子名称: Queuosine salvage protein DUF2419, 2-amino-5-({[(1S,4S,5R)-4,5-dihydroxycyclopent-2-en-1-yl]amino}methyl)-7-(5-O-phosphono-beta-D-ribofuranosyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: 7-deazaguanine salvage, queuosine, trna modification, hydrolase
• 由来する生物種: Sphaerobacter thermophilus DSM 20745
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75460.27

構造登録者

Hung, S.-H.,Swairjo, M.A. (登録日: 2022-04-04, 公開日: 2022-12-21, 最終更新日: 2023-10-25)

主引用文献

Hung, S.H.,Elliott, G.I.,Ramkumar, T.R.,Burtnyak, L.,McGrenaghan, C.J.,Alkuzweny, S.,Quaiyum, S.,Iwata-Reuyl, D.,Pan, X.,Green, B.D.,Kelly, V.P.,de Crecy-Lagard, V.,Swairjo, M.A.
Structural basis of Qng1-mediated salvage of the micronutrient queuine from queuosine-5'-monophosphate as the biological substrate.
Nucleic Acids Res., 51:935-951, 2023

PubMed Abstract: Eukaryotic life benefits from-and ofttimes critically relies upon-the de novo biosynthesis and supply of vitamins and micronutrients from bacteria. The micronutrient queuosine (Q), derived from diet and/or the gut microbiome, is used as a source of the nucleobase queuine, which once incorporated into the anticodon of tRNA contributes to translational efficiency and accuracy. Here, we report high-resolution, substrate-bound crystal structures of the Sphaerobacter thermophilus queuine salvage protein Qng1 (formerly DUF2419) and of its human ortholog QNG1 (C9orf64), which together with biochemical and genetic evidence demonstrate its function as the hydrolase releasing queuine from queuosine-5'-monophosphate as the biological substrate. We also show that QNG1 is highly expressed in the liver, with implications for Q salvage and recycling. The essential role of this family of hydrolases in supplying queuine in eukaryotes places it at the nexus of numerous (patho)physiological processes associated with queuine deficiency, including altered metabolism, proliferation, differentiation and cancer progression.

PubMed: 36610787
DOI: 10.1093/nar/gkac1231

実験手法

X-RAY DIFFRACTION (1.99 Å)