PA (influenza virus A)

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PA (influenza virus A)
other names
  • Polymerase acidic protein
  • RNA-directed RNA polymerase subunit P2

Existing structure data : PDB  2ZNL , PDB  4YYL , PDB  4ZHZ

Mass / length primary structure 716 amino acids , 82,588 Da
Identifier
External IDs
Enzyme classification
EC, category 3.1.-.-

PA ( polymerase acidic protein ) is an enzyme from influenza virus A. It is the enzymatic part of the viral RNA polymerase .

properties

PA is an internal protein of the IAV and occurs in the virion . It is one of the three viral proteins of the RNA polymerase complex alongside PB1 and PB2 . PA is a polymerase protein with an acidic isoelectric point , while PB1 and PB have a basic isoelectric point. Hence the abbreviation of the name. PA is phosphorylated .

The RNA polymerase complex is in the replication cycle for the replication and transcription of viral RNA in charge. The viral mRNA is transcribed using the unique cap snatching mechanism . The cellular mRNA modified with 5'-methylated cap structures are bound by PB2 to the 7-methylguanosine group and then cut by PA 10 to 13 nucleotides according to the cap structure . The short cap-bearing fragments are bound by PB1 and used in the RNA polymerase complex as primers for the transcription of viral RNA.

Applications

PA is being investigated as a target in drug development against IAV. Baloxavirmarboxil inhibits PA.

literature

  • J. Hu, X. Liu: Crucial role of PA in virus life cycle and host adaptation of influenza A virus. In: Medical microbiology and immunology. Volume 204, Number 2, April 2015, pp. 137-149, doi : 10.1007 / s00430-014-0349-y , PMID 25070354 .

Web links

Individual evidence

  1. ↑ MR Hilleman : Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control. In: Vaccine Volume 20, 2002, No. 25-26, pp. 3068-3087, PMID 12163258 .
  2. ↑ S. Massari, L. Goracci, J. Desantis, O. Tabarrini: Polymerase Acidic Protein-Basic Protein 1 (PA-PB1) Protein-Protein Interaction as a Target for Next-Generation Anti-Influenza Therapeutics. In: Journal of medicinal chemistry. Volume 59, Number 17, September 2016, pp. 7699-7718, doi : 10.1021 / acs.jmedchem.5b01474 , PMID 27046062 .
  3. ↑ H. Ju, J. Zhang, B. Huang, D. Kang, B. Huang, X. Liu, P. Zhan: Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives. In: Journal of medicinal chemistry. Volume 60, number 9, May 2017, pp. 3533-3551, doi : 10.1021 / acs.jmedchem.6b01227 , PMID 28118010 .