9SA4

Inhibition by ATP regulates the activity of a CBASS antiphage nucleotide cyclase

9SA4 の概要

• エントリーDOI: 10.2210/pdb9sa4/pdb
• 分子名称: CD-NTase, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: crispr cbass anti-viral immune anti-phage, antiviral protein
• 由来する生物種: Bacillus cereus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 158748.41

構造登録者

McMahon, S.A.,Gaskell-Mew, L.,Wotherspoon, P.,McQuarrie, S.,Graham, S.,Gloster, T.M.,White, M.F. (登録日: 2025-08-07, 公開日: 2026-08-05, 最終更新日: 2026-08-12)

主引用文献

Gaskell-Mew, L.,McQuarrie, S.,McMahon, S.A.,Wotherspoon, P.,Graham, S.,Gloster, T.M.,White, M.F.
Inhibition by ATP regulates the activity of a CBASS anti-phage nucleotide cyclase.
Biochem.J., 483:1617-1630, 2026

PubMed Abstract: The bacterial anti-phage immune system is complex, diverse, and in several important cases ancestral to that found in eukaryotes, including humans. One example is CBASS (cyclic oligonucleotide based anti-phage signalling system), a widespread bacterial defence that signals phage presence in the cell via cyclic nucleotide second messengers, activating ancillary effectors to combat infection. CBASS is homologous and ancestral to the eukaryotic cGAS/STING pathway for antiviral defence. The heart of the system is a nucleotide cyclase known as a cGAS/DncV-like nucleotidyltransferase, which is activated by phage infection. The mechanisms of activation of CBASS cyclases are diverse and in most cases not fully understood at a molecular level. Moreover, it is vital to keep these signal-generating enzymes fully inactive in the absence of phage infection to avoid auto-toxicity. Here, we report a structural and mechanistic study of a CBASS cyclase from Bacillus cereus. Using crystal structures of key reaction intermediates, coupled with kinetic analyses, we show that the substrate, ATP, plays a fundamental role in the inhibition of the non-activated form of the enzyme in vitro. We provide a molecular explanation for this regulation and explore the implications for the regulation of these important defence systems in bacterial immunity.

PubMed: 42496152
DOI: 10.1042/BCJ20260457

実験手法

X-RAY DIFFRACTION (2.23 Å)