GTP orchestrates CTP synthase via an allosteric effector-cycling mechanism.

GTP binds and dissociates from Drosophila melanogaster CTPS once per catalytic cycle, enabling the production of a single CTP molecule through an allosteric effector-cycling mechanism.

• Why it matters: Understanding how GTP drives CTP synthesis is crucial because CTP is essential for RNA and other biological processes, yet the precise regulatory mechanism remains unclear, limiting insights into nucleotide biosynthesis regulation.
• What they did: Researchers used cryo-EM structures, biochemical, and mutagenesis analyses to capture 34 distinct CTPS states at up to 2.0 Å resolution, revealing the GTP binding and dissociation cycle during catalysis.
• The result: The findings establish a detailed mechanistic framework showing GTP's obligatory binding and dissociation regulate CTP synthesis, highlighting a conserved allosteric regulation mode across life domains.