"Binding Site of Hexamethylene Amiloride in the SARS-CoV-2 Envelope Protein from Solid-state NMR"
Dr. Mei Hong, professor at MIT, discusses her group's recent work using diverse isotopic labeling patterns in solid-state NMR to determine the structure and drug binding site of the SARS-CoV-2 envelope protein. She explains how the envelope protein, a viroporin, impacts the virus lifecycle and pathogenicity. Dr. Hong details how her team determined the first structure of the envelope protein in lipid bilayers and how they created an "open state" of the protein to study its ion conduction activity. She discusses the use of isotopic labeling and mixing to determine inter-helical distances and orientations, and how they used fluorine-based distance measurements to solve the structure of the open state. Dr. Hong shares how they used various combinations of isotopic labeling to detect the binding of the drug hexamethylene amiloride to the protein, determining that one drug binds to the five-helix bundle from the lipid side. She proposes that the drug inhibits ion conduction by interfering with the gating mechanism of phenylalanines. Dr. Hong answers questions about why the virus would modify its sequence to slow down ion conduction and how solid-state NMR is particularly useful for studying small membrane proteins like viroporins.
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9 сен 2024
