title: Source of high pathogenicity of an avian influenza virus H5N1: why H5 is better cleaved by furin.
abstract: The origin of the 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 noninserted H5 and H3 bound to the furin (FR) active site. The cleavage loop of the highly pathogenic H5 was found to bind strongly to the FR 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: the arrangement of the catalytic triad, attachment of the catalytic Ser(368) 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 FR. The simulated data provide a clear answer to the question of why inserted H5 is better cleaved by FR than the other subtypes, explaining the high pathogenicity of avian influenza H5N1.
authors: Department of Chemistry, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330, Thailand.
authors: Panita
authors: P
authors: Decha
authors: Thanyada
authors: T
authors: Rungrotmongkol
authors: Pathumwadee
authors: P
authors: Intharathep
authors: Maturos
authors: M
authors: Malaisree
authors: Ornjira
authors: O
authors: Aruksakunwong
authors: Chittima
authors: C
authors: Laohpongspaisan
authors: Vudhichai
authors: V
authors: Parasuk
authors: Pornthep
authors: P
authors: Sompornpisut
authors: Somsak
authors: S
authors: Pianwanit
authors: Sirirat
authors: S
authors: Kokpol
authors: Supot
authors: S
authors: Hannongbua
mesh_terms: D003198:Computer Simulation; D045683:Furin / Q000737:chemistry* / Q000648:ultrastructure*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000648:ultrastructure*; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000472:pathogenicity* / Q000648:ultrastructure; D008956:Models, Chemical; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C109963:hemagglutinin, avian influenza A virus; D010447:Peptide Hydrolases; D045683:Furin