tetano
Editor, Senior Moderator
J Biol Chem. 2013 May 3. [Epub ahead of print]
The universal epitope of influenza A viral neuraminidase fundamentally contributes to enzyme activity and viral replication.
Doyle TM, Jaentschke B, Van Domselaar G, Hashem AM, Farnsworth A, Forbes NE, Li C, Wang J, He R, Brown EG, Li X.
Source
University of Ottawa, Canada;
Abstract
The only universally conserved sequence amongst all influenza A viral neuraminidase is located between amino acids 222-230. However, the potential roles of these amino acids (a.a.) remain largely unknown. Through an array of experimental approaches including mutagenesis, reverse genetics and growth kinetics, we found this sequence could markedly affect viral replication. Additional experiments revealed that enzymes with mutations in this region demonstrated substantially decreased catalytic activity, substrate-binding and thermostability. Consistent with viral replication analyses and enzymatic studies, protein modelling suggests that these amino acids could either directly bind to the substrate or contribute to the formation of the active site in the enzyme. Collectively, these findings reveal the essential role of this unique region in enzyme function and viral growth, which provides the basis for evaluating the validity of this sequence as potential target for antiviral intervention and vaccine development.
KEYWORDS:
Enzyme mutation, Epitope mapping, Influenza virus, Thermodynamics, Viral replication, influenza virus replication, neuraminidase, structural stability, substrate binding, universal epitope
PMID:
23645684
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23645684
The universal epitope of influenza A viral neuraminidase fundamentally contributes to enzyme activity and viral replication.
Doyle TM, Jaentschke B, Van Domselaar G, Hashem AM, Farnsworth A, Forbes NE, Li C, Wang J, He R, Brown EG, Li X.
Source
University of Ottawa, Canada;
Abstract
The only universally conserved sequence amongst all influenza A viral neuraminidase is located between amino acids 222-230. However, the potential roles of these amino acids (a.a.) remain largely unknown. Through an array of experimental approaches including mutagenesis, reverse genetics and growth kinetics, we found this sequence could markedly affect viral replication. Additional experiments revealed that enzymes with mutations in this region demonstrated substantially decreased catalytic activity, substrate-binding and thermostability. Consistent with viral replication analyses and enzymatic studies, protein modelling suggests that these amino acids could either directly bind to the substrate or contribute to the formation of the active site in the enzyme. Collectively, these findings reveal the essential role of this unique region in enzyme function and viral growth, which provides the basis for evaluating the validity of this sequence as potential target for antiviral intervention and vaccine development.
KEYWORDS:
Enzyme mutation, Epitope mapping, Influenza virus, Thermodynamics, Viral replication, influenza virus replication, neuraminidase, structural stability, substrate binding, universal epitope
PMID:
23645684
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23645684