Keys to Lipid Selection in Fatty Acid Amide Hydrolase Catalysis: Structural Flexibility, Gating Residues and Multiple Binding Pockets - Fig 3

<p><b>(A)</b> Statistical distribution (% over the total equilibrated conformations—reported as bar graphs) of anandamide (first row), oleamide (second row), and palmitoylethanolamide (PEA—third row) conformations when located in the MA (red bars), T (cyan bars), and AB (orange bars) regions of the <i>wt</i>FAAH (first column) and <i>mut</i>FAAH (second column) systems. For the <i>mut</i>FAAH/oleamide system, the percentage of unbounded oleamide conformations (NB—not-bound) is also indicated with a green bar. For each system, one representative conformation of the most populated state is shown. The MA (red) and AB (orange) channels are shown in molecular surfaces. Key residues of the FAAH active site are in space-filling representation, namely: Leu192 (gray), Phe194 (ice blue), Phe381 (maroon), Phe432 (green), and Trp531 (violet). Phe432 and Trp531 are mutated in Ala in the <i>mut</i>FAAH systems. The substrates (yellow), as well as the catalytic triad and the oxyanion hole (cyan) are also shown in sticks. <b>(B)</b> Percentages of pre-reactive conformations of anandamide, oleamide, and palmitoylethanolamide (in rows) in the MA, T, and AB regions (in columns) of the <i>wt</i>FAAH and <i>mut</i>FAAH systems. The total percentage of pre-reactive conformations over the production runs is also reported in the last column. A representative picture of pre-reactive conformation is also reported (full details are reported in the <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004231#pcbi.1004231.s014" target="_blank">S1 Text</a> and in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004231#pcbi.1004231.s007" target="_blank">S7 Fig</a>).