Figure 5.

VRR-Nuc Domain Phylogeny and Modelling

(A) PRALINE alignment of VRR-Nuc structures against FAN1 homologs overlaid with PSIPRED secondary structure predictions with α helices in red and β sheets in blue. The secondary structure of psNUC derived from the crystal structure is shown beneath. The position of the modeled helical insertion is shown above in light pink. Conserved catalytic residues are highlighted above.

(B) Phylogenetic tree showing VRR-Nuc domains, FAN1 orthologs, and archaeal HJC sequences.

(C) In silico modeling of the hFAN1 VRR-Nuc domain from the side (top) and top (bottom) colored according to the VRR-Nuc domain crystal structures. The predicted helical insertion is in light pink.

(D) Helical wheel Wenxian diagrams of helix 1 (left) and helix 2 (right) of the hFAN1 helical insertion clearly showing hydrophobic and hydrophilic faces of each helix.

(E) Electrostatic surface representation of the hFAN1 VRR-Nuc domain model in the same orientation as the bottom image in (C) showing the negatively charged active site (red) and positively charged DNA-binding surface (blue).