Human cytomegalovirus terminase complex (HCMV terminase complex)

The human cytomegalovirus (HCMV) terminase complex is a hetero-oligomeric viral enzyme essential for HCMV replication, composed primarily of the large subunit pUL56 (ATPase subunit responsible for DNA translocation and binding to packaging signals) and the small subunit pUL89 (nuclease subunit for site-specific DNA cleavage at pac motifs), with pUL51 as an accessory subunit required for complex assembly and nuclear localization. It processes head-to-tail concatemeric viral DNA into unit-length genomes by recognizing pac sequences in the terminal repeats, performing initial and terminal cleavages, and powering ATP-dependent translocation of DNA into preformed procapsids via the portal vertex. Absent in mammalian cells, this complex offers high specificity for antiviral targeting in HCMV infections, which cause severe morbidity in immunocompromised patients and congenitally infected newborns. Letermovir, a terminase inhibitor, blocks DNA packaging and is clinically approved for HCMV prophylaxis in transplant recipients, demonstrating potent activity without cross-reactivity to other herpesviruses. Structural studies reveal toroidal architectures for subunits and a curvilinear two-domain monomer for pUL89, with key motifs for nuclease activity (e.g., Asp463) and DNA binding (e.g., Arg544). Drug inhibition targets these functions, as seen with raltegravir binding the UL89 nuclease domain and experimental diketoacids disrupting activity.

Other names

HCMV terminasecytomegalovirus terminasepUL56-pUL89 complexterminase subunits pUL56/pUL89/pUL51

Inhibition of DNA cleavage and packaging, inhibition of nuclease activity, inhibition of ATPase activity