Related Experiment Video
Updated: Feb 10, 2026
Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
Published on: November 30, 2018
Crystal structure of the drug-resistant S31N influenza M2 proton channel
Jessica L Thomaston1, William F DeGrado1
1Department of Pharmaceutical Chemistry, University of California San Francisco, 555 Mission Bay Blvd. (S) Room 452V, San Francisco, California, 94158.
Abstract:
The M2 protein is a small proton channel found in the influenza A virus that is necessary for viral replication. The M2 channel is the target of a class of drugs called the adamantanes, which block the channel pore and prevent the virus from replicating. In recent decades mutations have arisen in M2 that prevent the adamantanes from binding to the channel pore, with the most prevalent of these mutations being S31N. Here we report the first crystal structure of the S31N mutant crystallized using lipidic cubic phase crystallization techniques and solved to 1.59 Å resolution. The Asn31 residues point directly into the center of the channel pore and form a hydrogen-bonded network that disrupts the drug-binding site. Ordered waters in the channel pore form a continuous hydrogen bonding network from Gly34 to His37.
Insights
The influenza A virus M2 protein S31N mutation prevents adamantane drugs from binding. This study provides the first crystal structure of the S31N mutant, revealing how it disrupts the drug-binding site.
Area of Science:
- Structural biology
- Virology
- Drug resistance
Background:
- The M2 protein is a proton channel essential for influenza A virus replication.
- Adamantane drugs target the M2 channel, but resistance mutations have emerged.
- The S31N mutation is the most common M2 resistance mutation.
Purpose of the Study:
- To determine the crystal structure of the S31N mutant influenza A virus M2 protein.
- To understand the structural basis of adamantane drug resistance.
Main Methods:
- Lipidic cubic phase crystallization techniques
- X-ray crystallography at 1.59 Å resolution
Main Results:
- The crystal structure of the S31N mutant M2 protein was determined.
- Asn31 residues directly interact with the channel pore, disrupting the adamantane binding site.
- Ordered water molecules form a hydrogen-bonding network within the pore.
Conclusions:
- The S31N mutation confers resistance to adamantanes by altering the M2 channel's drug-binding site.
- Structural insights into the S31N mutant M2 protein can inform the development of new antiviral strategies.
Related Concept Videos
02:42Ionic Crystal Structures
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
01:17Antiepileptic Drugs: Calcium Channel Blockers
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
01:08Antiepileptic Drugs: Sodium Channel Blockers
Sodium channel blockers modulate ion channels, particularly voltage-gated sodium channels. They block only sodium ion movement.
Among the most commonly prescribed antiepileptic drugs are...
01:20Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...
01:13Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers