16. CTP Synthetase and Related Enzymes

This chapter discusses the structure and chemistry of cytidine triphosphate (CTP) synthetase. CTP synthetase is an enzyme of four identical subunits, which is elegantly tailored for its particular needs. It utilizes glutamine as a nitrogen source and apparently has an active site in which the consecutive steps occur in a rapid, if not essentially concerted, manner. It would appear that the binding properties allow the simultaneous presence of glutamine, uridine triphosphate (UTP), and adenosine triphosphate (ATP) on the surface of the enzyme. This results in a rapid zipperlike effect in which a combination of conformational changes and nascent reactive compound's lead to high reactivity. The sequence would appear to be that the binding of ATP and UTP as well as the binding of guanosine triphosphate induces a conformational change into the formation of glutamyl enzyme and liberating nascent ammonia. Nascent ammonia then immediately attacks UTP before equilibrating with the medium leading to a UTP adduct. This, however, is highly reactive and reacts instantaneously with the adjacent ATP to form a phosphorylated intermediate, which then eliminates inorganic phosphate to form CTP. The conformational changes induced in the process are highly focused. The protein is designed to enhance the cooperativity pattern for the particular needs of the cell.