4I00

Crystal structure of influenza A neuraminidase N3-H274Y complexed with zanamivir

Summary for 4I00

• Entry DOI: 10.2210/pdb4i00/pdb
• Related: 3CKZ 4HZV 4HZW 4HZX 4HZY 4IZZ
• Descriptor: Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: neuraminidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Influenza A virus
• Cellular location: Host apical cell membrane ; Single-pass type II membrane protein : A9YN63
• Total number of polymer chains: 1
• Total formula weight: 44906.26

Authors

Li, Q.,Qi, J.,Vavricka, C.J.,Gao, G.F. (deposition date: 2012-11-16, release date: 2013-11-13, Last modification date: 2024-10-30)

Primary citation

Li, Q.,Qi, J.,Wu, Y.,Kiyota, H.,Tanaka, K.,Suhara, Y.,Ohrui, H.,Suzuki, Y.,Vavricka, C.J.,Gao, G.F.
Functional and structural analysis of influenza virus neuraminidase N3 offers further insight into the mechanisms of oseltamivir resistance.
J.Virol., 87:10016-10024, 2013

PubMed Abstract: The influenza virus neuraminidase H274Y substitution is a highly prevalent amino acid substitution associated with resistance to the most heavily used influenza drug, oseltamivir. Previous structural studies suggest that the group specific 252 residue (Y252 in group 1 and T252 in group 2) might be a key factor underlying H274Y resistance. However, H274Y has only been reported in N1 subtypes, which indicates that there must be additional key residues that determine H274Y resistance. Furthermore, we found that members of NA serotype N3 also possess Y252, raising the key question as to whether or not H274Y resistance may also be possible for some group 2 NAs. Here, we demonstrate that the H274Y substitution results in mild oseltamivir resistance for N3. Comparative structural analysis of N3, N1, and their 274Y variants indicates that the interaction of residue 296 (H in N1 and nonaromatic for other serotypes) with conserved W295 is another important determinant of oseltamivir resistance.

PubMed: 23824808
DOI: 10.1128/JVI.01129-13

Experimental method

X-RAY DIFFRACTION (1.6 Å)