8IDE

Structure of an ancient TsaD-TsaC-SUA5-TcdA modular enzyme (TsaN)

8IDE の概要

• エントリーDOI: 10.2210/pdb8ide/pdb
• EMDBエントリー: 35365
• 分子名称: N(6)-L-threonylcarbamoyladenine synthase, MANGANESE (II) ION (2 entities in total)
• 機能のキーワード: pandovirus salinus, tsan, modular enzyme, tc-amp, t6a, ct6a, viral protein
• 由来する生物種: Pandoravirus salinus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 211981.75

構造登録者

Zhang, Z.L.,Jin, M.Q.,Yu, Z.J.,Chen, W.,Wang, X.L.,Lei, D.S.,Zhang, W.H. (登録日: 2023-02-13, 公開日: 2023-07-26, 最終更新日: 2023-09-20)

主引用文献

Jin, M.,Zhang, Z.,Yu, Z.,Chen, W.,Wang, X.,Lei, D.,Zhang, W.
Structure-function analysis of an ancient TsaD-TsaC-SUA5-TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases.
Nucleic Acids Res., 51:8711-8729, 2023

PubMed Abstract: N 6-threonylcarbamoyladenosine (t6A) is a post-transcriptional modification found uniquely at position 37 of tRNAs that decipher ANN-codons in the three domains of life. tRNA t6A plays a pivotal role in promoting translational fidelity and maintaining protein homeostasis. The biosynthesis of tRNA t6A requires members from two evolutionarily conserved protein families TsaC/Sua5 and TsaD/Kae1/Qri7, and a varying number of auxiliary proteins. Furthermore, tRNA t6A is modified into a cyclic hydantoin form of t6A (ct6A) by TcdA in bacteria. In this work, we have identified a TsaD-TsaC-SUA5-TcdA modular protein (TsaN) from Pandoraviruses and determined a 3.2 Å resolution cryo-EM structure of P. salinus TsaN. The four domains of TsaN share strong structural similarities with TsaD/Kae1/Qri7 proteins, TsaC/Sua5 proteins, and Escherichia coli TcdA. TsaN catalyzes the formation of threonylcarbamoyladenylate (TC-AMP) using L-threonine, HCO3- and ATP, but does not participate further in tRNA t6A biosynthesis. We report for the first time that TsaN catalyzes a tRNA-independent threonylcarbamoyl modification of adenosine phosphates, leading to t6ADP and t6ATP. Moreover, TsaN is also active in catalyzing tRNA-independent conversion of t6A nucleoside to ct6A. Our results imply that TsaN from Pandoraviruses might be a prototype of the tRNA t6A- and ct6A-modifying enzymes in some cellular organisms.

PubMed: 37427786
DOI: 10.1093/nar/gkad587

実験手法

ELECTRON MICROSCOPY (3.21 Å)