MONDAY, Feb. 4 (HealthDay News) -- The three-dimensional structure of a portion of a flu protein targeted by drugs may provide the basis to counteract drug resistance and design new drugs, researchers report in the Jan. 31 issue of Nature.
Amanda L. Stouffer, Ph.D., from the University of Pennsylvania in Philadelphia, and colleagues solved the three-dimensional structure of the transmembrane-spanning region of the M2 protein, a pH-activated proton channel, from the influenza A virus in the presence (at low pH) and absence (at high pH) of amantadine, a drug that blocks the channel.
The researchers found that there were pH-dependent structural changes between the two structures near conserved histidine and tryptophan residues involved in proton gating. The amantadine-binding site was lined with amino acids that are mutated in amantadine-resistant viruses. They note that amantadine binding blocks the pore, which might lead to changes in the protonation state of the critical histidine.
"The crystallographic structures are in excellent agreement with a wide body of functional and spectroscopic data and provide a basis for the design of new inhibitors that target amantadine-resistant mutants of M2," Stouffer and colleagues conclude.
Competing financial interests have been declared by the study authors.
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