2LJC

Structure of the influenza AM2-BM2 chimeric channel bound to rimantadine

Summary for 2LJC

• Entry DOI: 10.2210/pdb2ljc/pdb
• Related: 2KIX 2KWX 2RLF 2ljb
• NMR Information: BMRB: 17929
• Descriptor: M2 protein, BM2 protein chimera, RIMANTADINE (2 entities in total)
• Functional Keywords: m2 channel, rimantadine binding, drug complex, transport protein, transport protein-inhibitor complex, transport protein/inhibitor
• Biological source: Influenza A virus, Influenza B virus
• Total number of polymer chains: 4
• Total formula weight: 15400.79

Authors

Pielak, R.M.,Oxenoid, K.,Chou, J.J. (deposition date: 2011-09-10, release date: 2011-11-16, Last modification date: 2024-05-01)

Primary citation

Pielak, R.M.,Oxenoid, K.,Chou, J.J.
Structural investigation of rimantadine inhibition of the AM2-BM2 chimera channel of influenza viruses.
Structure, 19:1655-1663, 2011

PubMed Abstract: The M2 channel of influenza A is a target of the adamantane family antiviral drugs. Two different drug-binding sites have been reported: one inside the pore, and the other is a lipid-facing pocket. A previous study showed that a chimera of M2 variants from influenza A and B that contains only the pore-binding site is sensitive to amantadine inhibition, suggesting that the primary site of inhibition is inside the pore. To obtain atomic details of channel-drug interaction, we determined the structures of the chimeric channel with and without rimantadine. Inside the channel and near the N-terminal end, methyl groups of Val27 and Ala30 from four subunits form a hydrophobic pocket around the adamantane, and the drug amino group appears to be in polar contact with the backbone oxygen of Ala30. The structures also reveal differences between the drug-bound and -unbound states of the channel that can explain drug resistance.

PubMed: 22078564
DOI: 10.1016/j.str.2011.09.003

Experimental method

SOLUTION NMR