tetano
Editor, Senior Moderator
J Biomol Struct Dyn. 2013 Sep 2. [Epub ahead of print]
Towards strain-independent anti-influenza peptides: a SAXS- and modeling-based study.
Pandey K, Rathore YS, Nath SK, Ashish.
Source
a CSIR-Institute of Microbial Technology , Chandigarh , 160036 , India.
Abstract
Using small angle X-ray scattering (SAXS) data, we reconstructed the scattering shape of the Hemagglutinin (HA) trimer protein from five different influenza strains. Comparison with the known crystal structures-based information aided in identifying volumes pertaining to the glycosylation in the HA trimers. By merging sequence information on HA proteins from pathogenic strains of influenza, we identified a novel druggable pocket composed of residues which remained conserved during evolution, lack propensity to be glycosylated, and play important role in maintaining interchain contacts in the pH-sensitive head group. To test our hypothesis that molecules reactive to this site may retard pH-induced opening of HA trimer in strain-independent manner, we performed in vitro screening of peptides representing interacting epitopes for their ability to retard pH-induced opening of HA trimers. Results brought forth that some of the 20 peptides tested can retard low pH-induced opening/association of HA proteins across different subtypes, thus propagating notion that the drug site and peptides identified here may pave way towards strain-independent anti-influenza molecules.
PMID:
23998328
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23998328
Towards strain-independent anti-influenza peptides: a SAXS- and modeling-based study.
Pandey K, Rathore YS, Nath SK, Ashish.
Source
a CSIR-Institute of Microbial Technology , Chandigarh , 160036 , India.
Abstract
Using small angle X-ray scattering (SAXS) data, we reconstructed the scattering shape of the Hemagglutinin (HA) trimer protein from five different influenza strains. Comparison with the known crystal structures-based information aided in identifying volumes pertaining to the glycosylation in the HA trimers. By merging sequence information on HA proteins from pathogenic strains of influenza, we identified a novel druggable pocket composed of residues which remained conserved during evolution, lack propensity to be glycosylated, and play important role in maintaining interchain contacts in the pH-sensitive head group. To test our hypothesis that molecules reactive to this site may retard pH-induced opening of HA trimer in strain-independent manner, we performed in vitro screening of peptides representing interacting epitopes for their ability to retard pH-induced opening of HA trimers. Results brought forth that some of the 20 peptides tested can retard low pH-induced opening/association of HA proteins across different subtypes, thus propagating notion that the drug site and peptides identified here may pave way towards strain-independent anti-influenza molecules.
PMID:
23998328
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23998328