9SAX
Inhibition by ATP regulates the activity of a CBASS antiphage nucleotide cyclase
Summary for 9SAX
| Entry DOI | 10.2210/pdb9sax/pdb |
| Descriptor | CD-NTase, [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-4-oxidanyl-oxolan-2-yl]methoxy-oxidanyl-phosphoryl] phosphono hydrogen phosphate, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | crispr cbass anti-viral anti-phage immune, antiviral protein |
| Biological source | Bacillus cereus |
| Total number of polymer chains | 4 |
| Total formula weight | 157258.54 |
| Authors | McMahon, S.A.,Gaskell-Mew, L.,Wotherspoon, P.,McQuarrie, S.,Graham, S.,Gloster, T.M.,White, M.F. (deposition date: 2025-08-08, release date: 2026-08-05, Last modification date: 2026-08-12) |
| Primary citation | 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 Cited by 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: 42496152DOI: 10.1042/BCJ20260457 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.83 Å) |
Structure validation
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