Binding of influenza A virus hemagglutinin to the sialoside receptor is not controlled by the homotropic allosteric effect.
Several sialoside receptors can bind to three active sites on influenza A viral hemagglutinin (HA), determining the mechanism of the virus and host cell binding. Optimization of complex structures at the molecular mechanics level shows an insignificant conformational change of HA between the isolated state and the complex with three sialosides. The energetic analysis of the HA (X-31, Aichi/2/1968)-sialoside complexes performed with quantum-mechanical calculations of the complex containing about 24 000 atoms at the FMO2-MP2/PCM/6-31G(d) level suggests that the binding of one, two, or three receptors has the same binding energy per sialoside, thus the trivalent HA-sialoside binding is not regulated by the sialoside homotropic allosteric effect. These results rationalize the experimentally reported simple binding mode for the trivalent HA-monovalent sialoside interaction in solution at equilibrium.
Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan. sawada-t@aist.go.jp
Toshihiko
T
Sawada
Dmitri G
DG
Fedorov
Kazuo
K
Kitaura
D000494:Allosteric Regulation; D020134:Catalytic Domain; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012794:Sialic Acids / Q000737:chemistry*; D013816:Thermodynamics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012794:Sialic Acids