37JY

Structure of PanS (DisA N-terminal domain) bound to cyclic UMP-AMP

This is a non-PDB format compatible entry.

Summary for 37JY

• Entry DOI: 10.2210/pdb37jy/pdb
• Descriptor: Panoptoo PanS synthase, 3'3'-cUMP-AMP (3 entities in total)
• Functional Keywords: anti-phage, synthase, antiviral protein
• Biological source: Rhizobium etli
• Total number of polymer chains: 6
• Total formula weight: 96430.56

Authors

Ragucci, A.E.,Haley, D.J.,Kranzusch, P.J. (deposition date: 2026-07-23, release date: 2026-09-09, Last modification date: 2026-10-21)

Primary citation

Ragucci, A.E.,Haley, D.J.,Kranzusch, P.J.
Bacterial diadenylate cyclase domains synthesize diverse nucleotide signals in anti-phage defense.
Biorxiv, 2026

PubMed Abstract: Bacterial diadenylate cyclase (DAC) enzymes synthesize the nucleotide signal 3'3' cyclic di-AMP (3'3'-c-di-AMP) to control osmoregulation, cell-wall homeostasis, and DNA-damage responses. Here we discover specialized roles for DAC enzymes in bacterial immunity and define a Panoptes-like system we name Panoptoo as a DAC-containing anti-phage defense that guards against viral immune evasion. The Panoptoo protein PanS is a minimal DAC that constitutively synthesizes 3'3' cyclic UMP-AMP (3'3'-cUA) or 3'3'-c-di-AMP to negatively regulate a partnering PanE S2TMβ membrane-targeting effector. We show that Panoptoo decoy signaling acts as a counter-defense to detect phage immune evasion proteins that inhibit nucleotide immune signals. A 1.5 Å crystal structure of PanS in complex with 3'3'-cUA explains how a symmetry break in the canonical DAC active site enables synthesis of asymmetric signaling molecules. Together, our results uncover a role for DAC domains in bacterial anti-phage defense and expand our understanding of nucleotide signaling in antiviral immunity.

PubMed: 42845585
DOI: 10.64898/2026.08.10.743927

Experimental method

X-RAY DIFFRACTION (1.51 Å)