Complexed Crystal Structure of Saccharomyces cerevisiae Dihydroorotase with Inhibitor 5-Fluoroorotate Reveals a New Binding Mode

Figure 3

New binding mode of 5-FOA. (a) The active site of ScDHOase with 5-FOA. (b) The active site of EcDHOase with 5-FOA (PDB entry 2EG8). The binding mode of 5-FOA to the active site is very similar to that of DHO. (c) The active site of huDHOase with 5-FOA (PDB entry 4C6M). By comparison, the bound 5-FOA by ScDHOase adopted the reverse orientation as compared to that in the active site of EcDHOase and huDHOase. (d) The loop-out binding mode of EcDHOase. (e) The loop-out binding mode of huDHOase. The flexible loop in EcDHOase and huDHOase is not involved in the binding of 5-FOA. (f) Superposition of the ScDHOase and EcDHOase complexes. Despite having a similar active site, the 5-FOA binding pose and the conformation of the catalytic loop of ScDHOase differ from those of EcDHOase.

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