Chiral influences of feedback inhibition with dCTP on murine deoxycytidine kinase.
The inhibitory effects of 4 kinds of 2'-deoxy-L-nucleoside 5'-triphosphates, which are enantiomers of natural dNTPs, on murine deoxycytidine kinase (dCK) were investigated. When ATP was used as the phosphate donor, L-dCTP showed significant inhibitory action noncompetitively and competitively with 2'-deoxycytidine (dCyd) and ATP, respectively. Thus L-dCTP, like dCTP, could serve as a feedback inhibitor for dCK. Recently, it has been demonstrated that human dCK can utilize L-dCyd as a substrate (Verri, A. et al. (1997) Mol. Pharmacol., 51, 132). The present results suggest that dCK is also unable to discriminate the chirality of nucleotides at the phosphate donor binding site of the enzyme.
Tomikawa
A
A
Department of Biological Sciences, Teikyo University of Science and Technology, Yamanashi, Japan.
Yamaguchi
T
T
Kawaguchi
T
T
Shudo
K
K
Saneyoshi
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003841:Deoxycytidine / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000737:chemistry / Q000494:pharmacology*; D005246:Feedback; D006801:Humans; D007700:Kinetics; D007941:Leukemia P388 / Q000201:enzymology; D051379:Mice; D013237:Stereoisomerism; D013379:Substrate Specificity; D016047:Zalcitabine / Q000031:analogs & derivatives / Q000494:pharmacology
D003845:Deoxycytosine Nucleotides; D003841:Deoxycytidine; C024107:2'-deoxycytidine 5'-triphosphate; D016047:Zalcitabine; D000255:Adenosine Triphosphate; D003842:Deoxycytidine Kinase