X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case
| Autor: | Lijun Liu, Nicholas F. Polizzi, Yibing Wu, William F. DeGrado, Jessica L. Thomaston, Jun Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Steric effects
Models Molecular Protein Conformation Nuclear Magnetic Resonance Adamantane Drug Resistance Crystal structure 010402 general chemistry Crystallography X-Ray 01 natural sciences Biochemistry Catalysis Article Viral Matrix Proteins chemistry.chemical_compound Colloid and Surface Chemistry Protein structure Models Drug Resistance Viral Side chain Amantadine Viral Nuclear Magnetic Resonance Biomolecular Crystallography Binding Sites biology Chemistry Hydrogen bond Prevention Molecular Hydrogen Bonding General Chemistry Nuclear magnetic resonance spectroscopy Hydrogen-Ion Concentration Influenza 3. Good health 0104 chemical sciences Infectious Diseases Emerging Infectious Diseases M2 proton channel Influenza A virus Chemical Sciences X-Ray Pneumonia & Influenza biology.protein Asparagine Biomolecular |
| Zdroj: | J Am Chem Soc Journal of the American Chemical Society, vol 141, iss 29 |
| ISSN: | 1520-5126 |
| Popis: | The amantadine-resistant S31N mutant of the influenza A M2 proton channel has become prevalent in currently circulating viruses. Here, we have solved an X-ray crystal structure of M2(22–46) S31N that contains two distinct conformational states within its asymmetric unit. This structure reveals the mechanism of adamantane resistance in both conformational states of the M2 channel. In the Inward(open) conformation, the mutant Asn31 side chain faces the channel pore and sterically blocks the adamantane binding site. In the Inward(closed) conformation, Asn31 forms hydrogen bonds with carbonyls at the monomer–monomer interface, which twists the monomer helices and constricts the channel pore at the drug binding site. We also examine M2(19–49) WT and S31Nusing solution NMR spectroscopy and show that distribution of the two conformational states is dependent on both detergent choice and experimental pH. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|