A. Desaizieu et al., ENZYMATIC CHARACTERIZATION OF BACILLUS-SUBTILIS GTP CYCLOHYDROLASE-I - EVIDENCE FOR A CHEMICAL DEPHOSPHORYLATION OF DIHYDRONEOPTERIN TRIPHOSPHATE, Biochemical journal, 306, 1995, pp. 371-377
GTP cyclohydrolase I catalyses the first committing step in the biosyn
thesis of the pterin moiety of folic acid: conversion of GTP to dihydr
oneopterin triphosphate. GTP cyclohydrolase I of Bacillus subtilis was
purified to homogeneity and shown to have a homo-octameric structure.
The enzyme had an apparent K-m for GTP of 4 mu M and, in the absence
of cations, a V-max of 80 nmol/min per mg of protein. K+ ions moderate
ly increased its V-max, whereas UTP and Ca2+ and Mg2+ ions drastically
increased its K-m for GTP. Dihydrofolate and other products of the fo
late and tetrahydrobiopterin pathways did not inhibit GTP cyclohydrola
se I. In addition to their effect on the enzyme activity, Ca2+ and Mg2
+ ions catalysed the chemical dephosphorylation of dihydroneopterin tr
iphosphate to non-cyclic dihydroneopterin monophosphate, the substrate
for the phosphomonoesterase reaction in folate biosynthesis. This dep
hosphorylation was specific and did not require the action of a phosph
atase. We suggest a physiological role for Ca2+ ions and UTP in regula
tion of folate biosynthesis at the levels of GTP cyclohydrolase I and
dephosphorylation of dihydroneopterin triphosphate.