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Biophys. J. BioFAST: First Published March 28, 2008. doi:10.1529/biophysj.107.127456
© 2008 by the Biophysical Society.

A more recent version of this article appeared on July 1, 2008.
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BIOPHYSICAL THEORY AND MODELING

Source of High Pathogenicity of an Avian Influenza Virus H5N1:Why H5 is Better Cleaved by Furin

Panita Decha 1, Thanyada Rungrotmongkol 1, Pathumwadee Intharathep 1, Mathuros Malaisree 1, Ornjira Aruksakunwong 2, Chittima Laohpongspaisan 1, Vudhichai Parasuk 1, Pornthep Sompornpisut 1, Somsak Pianwanit 1, Sirirat Kokpol 1 and Supot Hannongbua 1*

1 Chulalongkorn University
2 Rangsit University

* To whom correspondence should be addressed. E-mail: supot.h{at}chula.ac.th.

Submitted on December 25, 2007
Revised on January 24, 2008
Accepted on 5 March 2008


  Abstract
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.

Key Words: Furin, H5N1, Hemagglutinin, High pathogenicity, Molecular dynamics




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[Abstract] [Full Text] [PDF]


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Copyright © 2008 by the Biophysical Society.