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.

Abstract:

: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.

journal_name

Arch Virol

journal_title

Archives of virology

authors

Bhoye D,Cherian SS

doi

10.1007/s00705-017-3681-x

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

1031-1036

issue

4

eissn

0304-8608

issn

1432-8798

pii

10.1007/s00705-017-3681-x

journal_volume

163

pub_type

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