Extended Data Fig. 6: Structural analysis of poxin 2′,3′-cGAMP binding.
From: Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS–STING signalling
a, Overview of interactions in the VACV poxin–2′,3′-cGAMP complex that mediate substrate specificity. VACV poxin residues make three types of interactions with 2′,3′-cGAMP: sequence-specific contacts with the guanine base (left), hydrogen-bonding interactions with the 2′–5′ bond (middle) and sequence non-specific contacts with the adenine base (right). b, Simulated annealing omit maps showing electron density of 2′,3′-cGAMP before and after poxin cleavage. Base identities can clearly be assigned in both pre- and post-reactive structures. A clear gap exists in the post-reactive structure between the guanine 5′-OH and adenine 3′-phosphate confirming that the poxin product is Gp[2′–5′]Ap[3′]. c, tRNA splicing endoribonucleases are metal-independent enzymes that degrade ribonucleotide substrates through a 2′–3′-cyclic phosphate intermediate. These enzymes share the poxin catalytic triad composed of histidine, tyrosine and lysine, suggesting a related catalytic mechanism, despite the lack of sequence or structural homology.
