In silico analysis of the defensive potential of dGTPases in Wolbachia against viral infections through a molecular docking study
TL;DR
The Wolbachia dGTPase suggests a structural specialization that makes it particularly efficient in dGTP binding, suggesting a role in dNTP depletion as an antiviral mechanism.
Abstract
Introduction: Wolbachia is an endosymbiont that protects its host against viral infections, although the underlying mechanisms remain unclear. This in silico study explores the presence of antiviral defense systems in Wolbachia, with emphasis on dGTPases, enzymes that degrade dGTP, an essential nucleotide for viral replication. Methodology: Using PADLOC and DefenseFinder, 194 complete Wolbachia genomes were analyzed and defense systems were identified. The structures of dGTPases from Wolbachia, R. felis, S. putrefaciens and E. coli were predicted with Protenix and docked with dGTP using HADDOCK 2.4. Interactions were characterized with PLIP, affinity with PRODIGY‑LIG, and in silico mutagenesis was performed in E. coli. Results: The dGTPase system is present in 99% of strains carrying defense systems. The Wolbachia dGTPase showed the best HADDOCK score (-30.2), a very negative electrostatic energy (-128.1 kcal/mol) and a compact Mn²⁺ coordination (square planar, distances ≤2.44 Å) with three salt bridges. R. felis presented a similar score (-29.2) but a lower electrostatic component (-44.9 kcal/mol). The free‑living dGTPases (S. putrefaciens and E. coli) showed less favorable scores (-22.3 and -21.5). Mutagenesis (Phe391→Tyr, Glu400→Met) in E. coli did not reproduce the high affinity of Wolbachia. Conclusion: The Wolbachia dGTPase suggests a structural specialization that makes it particularly efficient in dGTP binding, suggesting a role in dNTP depletion as an antiviral mechanism.