A model of the full-length, membrane-bound human cytochrome P450 2C9, an enzyme essential for drug metabolism in the human liver, derived using an approach that combines coarse grained and atomic resolution molecular simulations (see Cojocaru et al., 10.1371/journal.pcbi.1002152). The protein backbone is shown by a green ribbon with two important loops (named "BC" and "FG") highlighted in mauve and blue, whereas the membrane is shown in orange. The lipid head groups are shown with blue and red balls to reveal the position of the positive (blue) and negative (red) charges on the lipids. Three different tunnels from the buried active site to the protein surface are shown by cyan, blue, and red tubes. The proposed substrate access tunnel from the membrane ("2a," cyan) is labeled with yellow arrows pointing towards the inside of the active site while two of the proposed product egress tunnels ("2c," blue; "S," red) are labeled with yellow arrows pointing away from the active site. A substrate molecule (the anti-inflammatory drug flurbiprofen) is overlaid on the membrane at the entrance of the proposed access tunnel, and its product is positioned above the membrane along one of the proposed egress tunnels. The active site is located adjacent to the heme group, shown in ball-and-stick representation colored by atom type. The image was generated with VMD (http://www.ks.uiuc.edu/Research/vmd/) and GIMP (http://www.gimp.org/).
Image Credit: Vlad Cojocaru, MPI for Molecular Biomedicine, Münster, Germany
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PLOS Computational Biology: published August 25, 2011 | https://doi.org/10.1371/journal.pcbi.1002147
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