FIGURE 1.

Structure, function, and regulation of eukaryotic IMPDHs. (a) Schematic and simplified scheme of the de novo purine nucleotide biosynthetic pathways. Competitive inhibitors are colored in yellow, while allosteric activators and inhibitors are colored in green and red, respectively. (b) Ribbon representation of an IMPDH tetramer, showing the catalytic domain (light blue) with the substrates NAD (yellow spheres) and IMP (orange spheres) and the regulatory Bateman domain (dark blue) with three GDP molecules (red spheres) bound. (c) Nucleotide binding to the allosteric sites in the Bateman domain promotes tetramer dimerization into octamers with different conformations and catalytic activities. IMPDH is represented as protein surface with the catalytic and regulatory domains light and dark blue colors, respectively. Adenine and guanine nucleotides bound to the Bateman regulatory domain are shown as spheres colored in green and red, respectively. IMPDH, IMP dehydrogenase