Phosphonoformic acid inhibits viral replication by trapping the closed form of the DNA polymerase.

ABSTRACT: Phosphonoformic acid (PFA, foscarnet) belongs to a class of antiviral drugs that inhibit the human cytomegalovirus DNA polymerase (UL54) by mimicking the pyrophosphate leaving group of the nucleotide transfer reaction. Difficulties expressing UL54 have hampered investigation of the precise structural requirements rendering inhibition by this drug. However, a previously engineered chimeric DNA polymerase, constructed by mutating the homologous polymerase from bacteriophage RB69 (gp43) to express several variable elements from UL54, can bypass this obstacle because of its favorable expression and acquired sensitivity to PFA (Tchesnokov, E. P., Obikhod, A., Schinazi, R. F., and Götte, M. (2008) J. Biol. Chem. 283, 34218-34228). Here, we compare two crystal structures that depict the chimeric

SUBMITTER: Zahn KE 

PROVIDER: S-EPMC3137095 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature