Ability of adenosine-2'(3')-deoxy-3'(2')-triphosphates and related analogues to replace ATP as phosphate donor for all human and Drosphila melanogaster deoxyribonucleoside kinases.
Six non-conventional adenosine-2'- and 3'-triphosphate analogues of ATP were tested as potential phosphate donors for all four human, and D. melanogaster, deoxyribonucleoside kinases. With dCK (only dAdo as acceptor), TK1, TK2 and dNK only 3'-deoxyadenosine-2'-triphosphate was an effective donor (5-60% that for ATP). With dCK (dCyd as acceptor) and dGK (dGuo as acceptor), sharing 45% sequence identity, donor activities ranged from 13 to 119% that for ATP. Products were 5'-phosphates. In some instances, kinetics are dependent on the nature of the acceptor, and donor and acceptors properties are mutually interdependent. Results are highly relevant to studies on the modes of interaction with the enzymes, and to interpretations of reported crystal structures of dCK and dNK with bound ligands.
Krawiec
Krzysztof
K
Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Warsaw, Poland.
Kierdaszuk
Borys
B
Kalinichenko
Elena N
EN
Rubinova
Elena B
EB
Mikhailopulo
Igor A
IA
Eriksson
Staffan
S
Munch-Petersen
Birgitte
B
Shugar
David
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003838:Deoxyadenine Nucleotides / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D013379:Substrate Specificity
C115030:2'-deoxyadenosine-3'-triphosphate; D003838:Deoxyadenine Nucleotides; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases; C026600:2'-deoxyadenosine triphosphate