tetano
Editor, Senior Moderator
Arch Virol. 2017 Dec 22. doi: 10.1007/s00705-017-3681-x. [Epub ahead of print]
[h=1]Computational analysis of the effect of polymerase acidic (PA) gene mutation F35L in the 2009 pandemic influenza A (H1N1) virus on binding aspects of mononucleotides in the endonuclease domain.[/h] Bhoye D[SUP]1[/SUP], Cherian SS[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] An F35L mutation in the N-terminal domain of the polymerase acidic protein (PA-Nter), which contains the active site of the endonuclease, has been reported to result in higher polymerase activity in mouse-adapted strains of the 2009 pandemic influenza A H1N1 virus. We modeled wild and mutant complexes of uridine 5'-monophosphate (UMP) as the endonuclease substrate and performed molecular dynamics simulations. The results demonstrated that the F35L mutation could result in a changed orientation of a helix containing active site residues and improve the ligand affinity in the mutant strain. This study suggests a molecular mechanism of enhanced polymerase activity.
PMID: 29273880 DOI: 10.1007/s00705-017-3681-x
[h=1]Computational analysis of the effect of polymerase acidic (PA) gene mutation F35L in the 2009 pandemic influenza A (H1N1) virus on binding aspects of mononucleotides in the endonuclease domain.[/h] Bhoye D[SUP]1[/SUP], Cherian SS[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] An F35L mutation in the N-terminal domain of the polymerase acidic protein (PA-Nter), which contains the active site of the endonuclease, has been reported to result in higher polymerase activity in mouse-adapted strains of the 2009 pandemic influenza A H1N1 virus. We modeled wild and mutant complexes of uridine 5'-monophosphate (UMP) as the endonuclease substrate and performed molecular dynamics simulations. The results demonstrated that the F35L mutation could result in a changed orientation of a helix containing active site residues and improve the ligand affinity in the mutant strain. This study suggests a molecular mechanism of enhanced polymerase activity.
PMID: 29273880 DOI: 10.1007/s00705-017-3681-x