Histidine 179 mutants of GTP cyclohydrolase I catalyze the formation of 2-amino-5-formylamino-8-ribofuranosylamino-4(3H)-pyrimidinone triphosphate

GTP cyclohydrolase I catalyzes the conversion of GTP to dihydroneopterin tr iphosphate. The replacement of histidine 179 by other amino acids affords m utant enzymes that do not catalyze the formation of dihydroneopterin tripho sphate. However, some of these mutant proteins catalyze the conversion of G TP to 2-amino-5-formylamino-6-ribofuranosylamino-4(3H) -pyrimidinone 5'-tri phosphate as shown by multinuclear NMR analysis. The equilibrium constant f or the reversible conversion of GTP to the ring-opened derivative is approx imately 0.1, The wild-type enzyme converts the formylamino pyrimidine deriv ative to dihydroneopterin triphosphate; the rate is similar to that observe d with GTP as substrate. The data support the conclusion that the formylami no pyrimidine derivative is an intermediate in the overall reaction catalyz ed by GTP cyclohydrolase I.