8XHR

Crystal structure of Mycobacterium tuberculosis MenT3 bound with CTP

8XHR の概要

• エントリーDOI: 10.2210/pdb8xhr/pdb
• 分子名称: Nucleotidyl transferase AbiEii/AbiGii toxin family protein, CYTIDINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: terminal nucleotidyltransferase, toxin, ctp, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 100619.87

構造登録者

Liu, J.,Yashiro, Y.,Tomita, K. (登録日: 2023-12-18, 公開日: 2024-02-28, 最終更新日: 2024-06-19)

主引用文献

Liu, J.,Yashiro, Y.,Sakaguchi, Y.,Suzuki, T.,Tomita, K.
Substrate specificity of Mycobacterium tuberculosis tRNA terminal nucleotidyltransferase toxin MenT3.
Nucleic Acids Res., 52:5987-6001, 2024

PubMed Abstract: Mycobacterium tuberculosis transfer RNA (tRNA) terminal nucleotidyltransferase toxin, MenT3, incorporates nucleotides at the 3'-CCA end of tRNAs, blocking their aminoacylation and inhibiting protein synthesis. Here, we show that MenT3 most effectively adds CMPs to the 3'-CCA end of tRNA. The crystal structure of MenT3 in complex with CTP reveals a CTP-specific nucleotide-binding pocket. The 4-NH2 and the N3 and O2 atoms of cytosine in CTP form hydrogen bonds with the main-chain carbonyl oxygen of P120 and the side chain of R238, respectively. MenT3 expression in Escherichia coli selectively reduces the levels of seryl-tRNASers, indicating specific inactivation of tRNASers by MenT3. Consistently, MenT3 incorporates CMPs into tRNASer most efficiently, among the tested E. coli tRNA species. The longer variable loop unique to class II tRNASers is crucial for efficient CMP incorporation into tRNASer by MenT3. Replacing the variable loop of E. coli tRNAAla with the longer variable loop of M. tuberculosis tRNASer enables MenT3 to incorporate CMPs into the chimeric tRNAAla. The N-terminal positively charged region of MenT3 is required for CMP incorporation into tRNASer. A docking model of tRNA onto MenT3 suggests that an interaction between the N-terminal region and the longer variable loop of tRNASer facilitates tRNA substrate selection.

PubMed: 38485701
DOI: 10.1093/nar/gkae177

実験手法

X-RAY DIFFRACTION (2.1 Å)