Structure-function studies of the influenza virus RNA polymerase PA subunit.
The influenza virus RNA-dependent RNA polymerase is a heterotrimeric complex (PA, PB1 and PB2) with multiple enzymatic activities for catalyzing viral RNA transcription and replication. The roles of PB1 and PB2 have been clearly defined, but PA is less well understood. The critical role of the polymerase complex in the influenza virus life cycle and high sequence conservation suggest it should be a major target for therapeutic intervention. However, until very recently, functional studies and drug discovery targeting the influenza polymerase have been hampered by the lack of three-dimensional structural information. We will review the recent progress in the structure and function of the PA subunit of influenza polymerase, and discuss prospects for the development of anti-influenza therapeutics based on available structures.
Liu
Yingfang
Y
National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Lou
Zhiyong
Z
Bartlam
Mark
M
Rao
Zihe
Z
D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009975:Orthomyxoviridae / Q000201:enzymology*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
D021122:Protein Subunits; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases