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

Figure 1

Comparison of DHOases. (a) The gene products for the first three reactions of pyrimidine biosynthesis are different among species. The higher eukaryotic human CAD consists of DHOase, CPSase, and ATCase domains fused covalently. Bacterial DHOase, CPSase, and ATCase function separately. However, CPSase and ATCase activities in S. cerevisiae are present in a single bifunctional protein, Ura2. Ura2 is a CAD-like polypeptide that contains a defective DHOase-like domain. (b) Sequence alignment of the flexible loop. The amino acids that are involved in catalysis are in red. The sequence composition and the length of these flexible loops are significantly distinct.

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