INFLUENZA A SUBTYPE N2 NEURAMINIDASE
The symptoms of infection with the common cold virus and with influenza virus are so similar that one often mistakes a cold for a flu. However, influenza virus infection is a much more severe disease, having killed millions of people at the beginning of the 20th century during the Spanish Flu epidemic. Vaccination against influenza virus is possible, but since the virus mutates quickly the effect of vaccination is only limited. Different influenza viruses are usually characterized by the type of two proteins that are expressed: hemagglutinin and neuraminidase. The Spanish Flu epidemic for instance was caused by a H1N1 strain of the virus, meaning this virus carried hemagglutinin H1 and neuraminidase N1. Altogether 12 types of hemagglutinin and 9 types of neuraminidase have been observed, H1, H2, H3, N1 and N2 among them in humans.
The structure here shows a molecule of neuraminidase together with a small aromatic compound, 4-(acetylamino)-3-hydroxy-5-nitro benzoic acid (BANA105). Like other such compounds it binds in the active site of neuraminidase. It is known that in the active site 11 amino acid residues remain unchanged, while other may vary between strains. The goal of the detailed structure analysis of neuraminidase, complexed with inhibitors like BANA105, is to find drug compounds that specifically interact with the conserved amino acids in the active site. While so far known inhibitors are not very effective, structure-based drug design based on the atomic structure of neuraminidase may help in finding effective inhibitors that may be used as drugs against various strains of influenza.
Protein Data Bank (PDB)
Jedrzejas, M.J. Singh, S. Brouillette, W.J. Laver, W.G. Air, G.M. Luo, M.; "Structures of aromatic inhibitors of influenza virus neuraminidase."; Biochemistry; (1995) 34:3144-3151 PubMed:7880809.
author: Arno Paehler