Description
Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis and relies on nucleotide metabolism for survival. Guanylate kinase (GK) catalyzes the reversible conversion of GMP and ATP to GDP and ADP, supporting purine salvage and maintaining GTP levels essential for DNA, RNA, and protein synthesis. This study characterizes A. phagocytophilum guanylate kinase (ApGK) to evaluate its potential as a selective drug target. X-ray crystallography revealed conserved CORE, LID, and GMP-binding domains typical of GKs. However, ApGK shares only ~33% similarity with human GK, indicating structural divergence. Active-site comparisons highlight distinct residue differences that support species-specific targeting. Ligand-binding analysis confirmed conserved interactions with GMP, ATP (ADP), and K⁺, demonstrating catalytic competence. Structural data also suggest ApGK forms a functional dimer. Overall, ApGK retains canonical GK features while exhibiting differences that position it as a promising and selective antimicrobial target.