New functional domains of human cytomegalovirus pUL89 predicted by sequence analysis and three-dimensional modelling of the catalytic site DEXDc.
BACKGROUND
Benzimidazole D-ribonucleosides inhibit DNA packaging during human cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56 and pUL89, the large and small subunits of the HCMV terminase respectively, their mechanism of action is not yet fully understood.


RESULTS
To better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives, we studied the HCMV pUL89 protein by a genetic approach combined with primary structure analysis. The pUL89 sequence analysis of 25 HCMV strains and counterparts among herpesviruses allowed identification of 12 conserved regions. We also built a three-dimensional model of the pUL89 ATPasic catalytic site, including ATPase motor motifs 1, II and III, that may facilitate the development of future antiviral drugs active against HCMV. Finally, we identified several putative functional domains in pUL89, such as pUL89 zinc finger (pUL89-ZF), DNA cutting sites and portal binding sites, that are probably involved in CMV DNA cleavage and packaging.
Champier
Gaël
G
EA MENRT 3175 Faculté de Médecine de Limoges et Laboratoire de Bactériologie-Virologie, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
Hantz
Sébastien
S
Couvreux
Anthony
A
Stuppfler
Stéphanie
S
Mazeron
Marie-Christine
MC
Bouaziz
Serge
S
Denis
François
F
Alain
Sophie
S
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D017124:Conserved Sequence; D003587:Cytomegalovirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D042003:DNA Packaging / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism*; D015195:Drug Design; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D016335:Zinc Fingers
D000998:Antiviral Agents; D004279:DNA, Viral; C436448:UL89 protein, Cytomegalovirus; D014764:Viral Proteins; D004706:Endodeoxyribonucleases; D000251:Adenosine Triphosphatases