Sandbox 111: Difference between revisions

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Student, Lynmarie K Thompson, Joel L. Sussman

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 '''Drug Binding Site'''
-Amantadine binds with high affinity to a site in the M2 protein spanning five residues: Leu 26, Val 27, Ala 30, Ser 31, and Gly 34.  This high affinity is seen at pH’s closer to neutral.  In lower pH’s the protein is only somewhat bound to amantadine.  Therefore, when determining the mechanism by which amantadine blocks the channel experiments must be conducted at neutral pH.  <scene name='Sandbox_111/Binding/10'>Binding of amantadine</scene> to the M2 protein is illustrated for viewing of the bonds that form.
+'''Additional Features'''
+<scene name='Sandbox_111/His37/1'>His37</scene> – His37 has been found to exhibit significant proton selectivity.  This suggests that His37 is involved in the opening of the conductive channel.  The channel is non-conductive when His37 is not protonated, and conductive when it is in the protonated state (Pielak/Chou).
+<scene name='Sandbox_111/Trp41_ring/1'>Trp41</scene> – Replacing Trp41 with a substitute amino acid results in increased channel current in in both directions.  As such, the Trp 41 site is important to directional selectivity, in that it regulates the direction of the proton channel flow.  This is accomplished in part because it forms a ring that prevents water from entering the channel and reaching the His37, and thus protonating if the pH is high, from the C-terminus(Pielak/Chou).
+In addition, the proton transport channel is used to equalize the pH in the channel with that of the cytoplasm in the host cell.  This prevents rearrangement of the haemmagglutanin during its transport to the host cell. (Schnell)
-'''Additional Features'''
 '''Credits'''
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 Stephenson I, Nicholson KG. Influenza: vaccination and treatment. Eur Respir J 2001; 17: 1282-93.
+Pielak RM, Chou JJ.  "Infuenza M2 proton channels".  BBAMEM-80262; No. of pages: 8; 4C: 2, 3, 5, 6.