title: Utility of the bacteriophage RB69 polymerase gp43 as a surrogate enzyme for herpesvirus orthologs.
abstract: Viral polymerases are important targets in drug discovery and development efforts. Most antiviral compounds that are currently approved for treatment of infection with members of the herpesviridae family were shown to inhibit the viral DNA polymerase. However, biochemical studies that shed light on mechanisms of drug action and resistance are hampered primarily due to technical problems associated with enzyme expression and purification. In contrast, the orthologous bacteriophage RB69 polymerase gp43 has been crystallized in various forms and therefore serves as a model system that provides a better understanding of structure-function relationships of polymerases that belong the type B family. This review aims to discuss strengths, limitations, and opportunities of the phage surrogate with emphasis placed on its utility in the discovery and development of anti-herpetic drugs.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bennett
authors.forename: Matthias
authors.initials: M
authors.lastname: Götte
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006564:Herpesviridae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006566:Herpesviridae Infections / Q000821:virology*; D006801:Humans; D008958:Models, Molecular; D019384:Nucleic Acid Synthesis Inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase