Fig. 6: Structural insights into the Arg-specific macrodomains defined by DUF4804.

A Topology diagrams of TcPARG, MavL, CG2909, CG3568, and Larg1. A similar macrodomain core arrangement among these enzymes is observed and highlighted in cyan rectangles. The di-phosphate binding loops, catalytic loops, common structural insertions, and variable regions in Arg-specific macrodomains are highlighted in red, green, yellow, and gray, respectively. B Superposition of MavL (gray) and TcPARG (teal, PDB: 3SIG) showing the loop spanning Q103 to T115 in MavL as an insertion that is absent in TcPARG. C Superposition of MavL (gray), CG2909 (salmon), CG3568 (yellow), and Larg1 (magenta, PDB: 7W3S) showing the common insertions in these Arg-specific macrodomains. D A hydrophobic residue found at the same position in Arg-specific macrodomain insertions. E Interactions of ADPR distal ribose with MavL, CG2909, CG3568, and Larg1 suggest a similar distal ribose binding feature. Note that MavL, CG3568, and Larg1 harbor a glutamate residue (E107 in MavL, E237 in CG3568, and E160 in Larg1) at the same position that does not interact directly with the distal ribose. F Interactions of ADPR adenosine with MavL, CG2909, CG3568, and Larg1. Adenosines in MavL, CG2909, and CG3568 are sandwiched between two residues and stabilized by π-π (in MavL) or π-π and π-cation (in CG2909 and CG3568) interactions. In Larg1, the adenosine is positioned by the N6-D351 interaction and the steric restriction provided by Y134.