CTP synthase catalyzes the last committed step in de novo pyrimidinenucleotide
biosynthesis. Active CTP synthase is a tetrameric enzyme composed
of a dimer of dimers. The tetramer is favoured in the presence of the substrate
nucleotides ATP and UTP; when saturated with nucleotide, the tetramer
completely dominates the oligomeric state of the enzyme. Furthermore,
phosphorylation has been shown to regulate the oligomeric states of the
enzymes from yeast and human. The crystal structure of a dimeric form of CTP
synthase from Sulfolobus solfataricus has been determined at 2.5 A ° resolution.
A comparison of the dimeric interface with the intermolecular interfaces in the
tetrameric structures of Thermus thermophilus CTP synthase and Escherichia
coli CTP synthase shows that the dimeric interfaces are almost identical in the
three systems. Residues that are involved in the tetramerization of S. solfataricus
CTP synthase according to a structural alignment with the E. coli enzyme all
have large thermal parameters in the dimeric form. Furthermore, they are seen
to undergo substantial movement upon tetramerization.