7OVO

Heterodimeric murine tRNA-guanine transglycosylase in complex with queuine

7OVO の概要

• エントリーDOI: 10.2210/pdb7ovo/pdb
• 分子名称: Queuine tRNA-ribosyltransferase accessory subunit 2, Queuine tRNA-ribosyltransferase catalytic subunit 1, ZINC ION, ... (7 entities in total)
• 機能のキーワード: transferase, transglycosylase, tim barrel, dimer, tgt
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91298.12

構造登録者

Sebastiani, M.,Heine, A.,Reuter, K. (登録日: 2021-06-15, 公開日: 2022-06-22, 最終更新日: 2024-02-07)

主引用文献

Sebastiani, M.,Behrens, C.,Dorr, S.,Gerber, H.D.,Benazza, R.,Hernandez-Alba, O.,Cianferani, S.,Klebe, G.,Heine, A.,Reuter, K.
Structural and Biochemical Investigation of the Heterodimeric Murine tRNA-Guanine Transglycosylase.
Acs Chem.Biol., 17:2229-2247, 2022

PubMed Abstract: In tRNA, tRNA, tRNA, and tRNA of most bacteria and eukaryotes, the anticodon wobble position may be occupied by the modified nucleoside queuosine, which affects the speed and the accuracy of translation. Since eukaryotes are not able to synthesize queuosine de novo, they have to salvage queuine (the queuosine base) as a micronutrient from food and/or the gut microbiome. The heterodimeric Zn containing enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into the above-named tRNAs in exchange for the genetically encoded guanine. This enzyme has attracted medical interest since it was shown to be potentially useful for the treatment of multiple sclerosis. In addition, TGT inactivation via gene knockout leads to the suppressed cell proliferation and migration of certain breast cancer cells, which may render this enzyme a potential target for the design of compounds supporting breast cancer therapy. As a prerequisite to fully exploit the medical potential of eukaryotic TGT, we have determined and analyzed a number of crystal structures of the functional murine TGT with and without bound queuine. In addition, we have investigated the importance of two residues of its non-catalytic subunit on dimer stability and determined the Michaelis-Menten parameters of murine TGT with respect to tRNA and several natural and artificial nucleobase substrates. Ultimately, on the basis of available TGT crystal structures, we provide an entirely conclusive reaction mechanism for this enzyme, which in detail explains why the TGT-catalyzed insertion of some nucleobases into tRNA occurs reversibly while that of others is irreversible.

PubMed: 35815944
DOI: 10.1021/acschembio.2c00368

実験手法

X-RAY DIFFRACTION (2.1 Å)