Detail of "1425-63-4"

Reference

The pH-dependence of the reaction catalyzed by dihydrofolate reductase from Escherichia coli

The pH-dependence of the reaction catalyzed by dihydrofolate reductase from Escherichia coli. Stone, Stuart R. (John Curtin Sch. Med. Res., Aust. Natl. Univ., Canberra 2601, Australia). Biochem. Soc. Trans., 11(2), 184-5 (English) 1983. CODEN: BCSTB5. ISSN: 0300-5127. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) A pK value of ~8.In this article, certain chemicals are used. Some of their cas registry numbers are 9002-03-3 and 1425-63-4 0 was detd. from the pH dependence of kinetic parameters (Vmax, Vmax/Km, Kd) of E. coli dihydrofolate reductase (EC 1.5.1.3) (I) for a group on I important in the binding of dihydrofolate and the substrate analog, 2,4-diamino-6,7-dimethylpteridine, an inhibitor. Heat of ionization studies suggested that the group responsible for the pK of 8.0 may be a carboxyl group. Previous x-ray crystallog. studies of the ternary complex, I-NADPH-methotrexate, indicated that the b-carboxyl group of asparagine-27 in E. coli I, which is close to the N-1 atom of methotrexate, is also situated in an extremely hydrophobic environment and thus could be responsible for the pK of 8.0 obsd. in the pH profiles. It is proposed that the pteridine is bound in its neutral form and subsequently protonated by the asparagine-27 carboxyl group; the pos. charge on the pteridine (in the case of dihydrofolate, the N-5 atom) would then be stabilized by the proximity of the now neg.-charged carboxylate group. Such protonation of the N-5 atom of dihydrofolate would facilitate redn. of the N-5:C-6 double bond to form tetrahydrofolate. .