GTP cyclohydrolase II (GCHII)

GTP cyclohydrolase II (GCHII) is a key enzyme that catalyzes the first committed and rate-limiting step in the biosynthesis of riboflavin (vitamin B2) in bacteria, plants, and fungi. It converts GTP into 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate, formate, and pyrophosphate. Because the riboflavin biosynthetic pathway is essential for many pathogens but entirely absent in humans, GCHII is a highly attractive target for the development of novel, selective antimicrobial and antifungal agents. Inhibition of GCHII leads to riboflavin deficiency, which impairs pathogen growth and reduces their ability to detoxify host-derived reactive nitrogen species, such as nitric oxide. While no clinical drugs currently target GCHII, structural studies using substrate analogs like GMPCPP have provided a foundation for rational drug design.

Other names

GTP cyclohydrolase-2Guanosine triphosphate cyclohydrolase IIGTP-8-formylhydrolaseRibARIB1

Inhibition of the first committed step of riboflavin biosynthesis, leading to riboflavin auxotrophy and increased susceptibility to host-derived nitrosative stress.