Sally Furniss
Well-known member
Source of High Pathogenicity of an Avian Influenza Virus H5N1:Why H5 is Better Cleaved by Furin.
<!--AuthorList-->Decha P, Rungrotmongkol T, Intharathep P, Malaisree M, Aruksakunwong O, Laohpongspaisan C, Parasuk V, Sompornpisut P, Pianwanit S, Kokpol S, Hannongbua S.
Chulalongkorn University.
Origin of high pathogenicity of an emerging avian influenza H5N1 due to the -RRRKK- insertion at the cleavage loop of the hemagglutinin H5, was studied using the molecular dynamics technique, in comparison with those of the non-inserted H5 and H3 bound to furin active site. The cleavage loop of the highly pathogenic H5 was found to bind strongly to the furin cavity, serving as a conformation suitable for the proteolytic reaction. With this configuration, the appropriate interatomic distances were found for all three reaction centers of the enzyme-substrate complex: there are the arrangement of the catalytic triad, attachment of the catalytic Ser368 to the reactive S1-Arg, and formation of the oxyanion hole. Experimentally, the -RRRKK- insertion was also found to increase in cleavage of hemagglutinin by furin. The simulated data provide a clear answer to the question of why inserted H5 is better cleaved by furin than the other subtypes, explaining the high pathogenicity of avian influenza H5N1.
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
<!--AuthorList-->Decha P, Rungrotmongkol T, Intharathep P, Malaisree M, Aruksakunwong O, Laohpongspaisan C, Parasuk V, Sompornpisut P, Pianwanit S, Kokpol S, Hannongbua S.
Chulalongkorn University.
Origin of high pathogenicity of an emerging avian influenza H5N1 due to the -RRRKK- insertion at the cleavage loop of the hemagglutinin H5, was studied using the molecular dynamics technique, in comparison with those of the non-inserted H5 and H3 bound to furin active site. The cleavage loop of the highly pathogenic H5 was found to bind strongly to the furin cavity, serving as a conformation suitable for the proteolytic reaction. With this configuration, the appropriate interatomic distances were found for all three reaction centers of the enzyme-substrate complex: there are the arrangement of the catalytic triad, attachment of the catalytic Ser368 to the reactive S1-Arg, and formation of the oxyanion hole. Experimentally, the -RRRKK- insertion was also found to increase in cleavage of hemagglutinin by furin. The simulated data provide a clear answer to the question of why inserted H5 is better cleaved by furin than the other subtypes, explaining the high pathogenicity of avian influenza H5N1.
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum