Dear All,
In the latest Nature (which for once arrived in a few days to our
office...) there are interesting structures of the influenza M2
proton channel.
One is by NMR, which resulted in a model of a closed state with four
inhibitor molecules bound to the outside. Another is by X-ray
crystallography, where an open state is observed. The x-ray structure
is at 2 Angstrom without inhibitor, and they include a complex with
the inhibitor at 3.5 Angstrom, where the inhibitor is modelled in
positive difference density inside the pore. Drug-resistant mutations
are near the binding site proposed in the X-ray paper, but the
resolution
is limited (3.5 Angstrom). The NMR paper also explains the drug-
resistant mutations, but perhaps less convincingly. With the current
evidence, which is more convincing? Or could both be "true"? Of
course, we can always say we should wait for more evidence, like a
higher-resolution X-ray structure or more biochemical data. In any
case, I am curious to hear the opinions of other structural biologists.
Carnaval greetings,
Mark van Raaij
