Why does avian influenza A virus hemagglutinin bind to avian receptor stronger than to human receptor? Ab initio fragment molecular orbital studies

Biochem Biophys Res Commun. 2006 Dec 8;351(1):40-3. doi: 10.1016/j.bbrc.2006.09.165. Epub 2006 Oct 12.

Abstract

Influenza A viruses attach to alpha-sialosides on the target cell surface by their hemagglutinins, which strictly recognize the difference in sialic acid-galactose linkage. Why does avian virus H3 subtype bind to avian receptor Neu5Ac(alpha2-3)Gal stronger than to human receptor Neu5Ac(alpha2-6)Gal? Why does avian H3 mutated Gln226 to Leu preferentially bind to human receptor? In this paper, we theoretically answer the questions by molecular mechanics and ab initio fragment molecular orbital (FMO) calculations. The binding energy between avian H3 and avian receptor is 8.2kcal/mol larger than that of the avian H3-human receptor complex estimated at the FMO-HF/STO-3G level, which is a reason that avian H3 binds to avian receptor stronger than to human receptor. Avian Leu226 H3 clashes to Gal unit on the avian receptor to quite decrease its binding affinity. In contrast, Gal unit on the human receptor forms intermolecular hydrophobic interaction with avian Leu226 H3 to afford moderate binding affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Birds
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / ultrastructure*
  • Humans
  • Models, Chemical*
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation
  • Receptors, Cell Surface / chemistry*
  • Structure-Activity Relationship

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Cell Surface
  • hemagglutinin, avian influenza A virus
  • hemagglutinin, human influenza A virus