Structural and Functional Analysis of Laninamivir and its Octanoate Prodrug Reveals Group Specific Mechanisms for Influenza NA Inhibition
Figure 5
Comparison of oseltamivir (yellow), laninamivir octanoate (magenta) and laninamivir (turquoise) binding to p09N1.
Laninamivir binds to p09N1 with a similar active site conformation to the uncomplexed structure. Both laninamivir octanoate and oseltamivir binding to p09N1 induces rotation of Glu276 toward Arg224 where they form a salt bridge. This Glu276 rotation creates a hydrophobic pocket that accommodates the hydrophobic pentyl ether side chain of oseltamivir, however results in a weaker overall binding mode of laninamivir octanoate. The terminal carbon of the oseltamivir side chain is 3.73 Å from the hydrophobic Glu276 Cβ.