title: Conserved domains and structure prediction of human cytomegalovirus UL27 protein.
abstract: BACKGROUND
  The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine-threonine kinase, UL97 protein (pUL97). Because maribavir-resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear.
  
  
  METHODS
  As there is no available crystal structure for pUL27 or any known structures of its homologous proteins, we attempted to identify pUL27 functional domains by sequence analysis, identification of conserved domains, structure prediction and matching with previously known maribavir resistance mutations.
  
  
  RESULTS
  The UL27 sequence analysis of 20 HCMV wild-type strains and 8 ganciclovir-resistant HCMV strains allowed us to describe four conserved domains, to localize the putative phosphorylation sites and to identify protein-protein interface domains, suggesting that pUL27 could interact with either pUL97 or itself.
  
  
  CONCLUSIONS
  Although the function of pUL27 is still unknown in the HCMV replication cycle, our approach identified target domains that appeared to be essential to the function of pUL27. This work provides a better understanding on the relative importance of each pUL27 mutation and could form the basis of later comparison analyses, when a three-dimensional structure of a pUL27 homologue will be available.
authors.affiliation: Centre National de Référence des Cytomégalovirus, Université de Limoges, EA3175, INSERM, Equipe Avenir, Limoges, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hantz
authors.forename: Anthony
authors.initials: A
authors.lastname: Couvreux
authors.forename: Gaël
authors.initials: G
authors.lastname: Champier
authors.forename: Laurène
authors.initials: L
authors.lastname: Trapes
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cotin
authors.forename: François
authors.initials: F
authors.lastname: Denis
authors.forename: Serge
authors.initials: S
authors.lastname: Bouaziz
authors.forename: Sophie
authors.initials: S
authors.lastname: Alain
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D017124:Conserved Sequence / Q000235:genetics*; D003587:Cytomegalovirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D012263:Ribonucleosides / Q000494:pharmacology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole