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.
Arch Virol
; 163(4): 1031-1036, 2018 Apr.
Article
in En
| MEDLINE
| ID: mdl-29273880
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.
Full text:
1
Database:
MEDLINE
Main subject:
Uridine Monophosphate
/
RNA-Dependent RNA Polymerase
/
Viral Nonstructural Proteins
/
Endonucleases
/
Influenza A Virus, H1N1 Subtype
/
Mutation
Limits:
Animals
/
Humans
Language:
En
Journal:
Arch Virol
Year:
2018
Type:
Article
Affiliation country:
India