A. Sillero et Mag. Sillero, Synthesis of dinucleoside polyphosphates catalyzed by firefly luciferase and several ligases, PHARM THERA, 87(2-3), 2000, pp. 91-102
The findings presented here originally arose from the suggestion that the s
ynthesis of dinucleoside polyphosphates (NpnN) may be a general process inv
olving enzyme ligases catalyzing the transfer of a nucleotidyl moiety via n
ucleotidyl-containing intermediates, with release of pyrophosphate. Within
this context, the characteristics of the following enzymes are presented. F
irefly luciferase (EC 1.12.13.7), an oxidoreductase with characteristics of
a ligase, synthesizes a variety of (di)nucleoside polyphosphates with four
or more inner phosphates. The discrepancy between the kinetics of light pr
oduction and that of NpnN synthesis led to the finding that E.L-AMP (L = de
hydroluciferin), formed from the E.LH2-AMP complex (LH2 = luciferin) shortl
y after the onset of the reaction, was the main intermediate in the synthes
is of (di)nucleoside polyphosphates. Acetyl-CoA synthetase (EC 6.2.1.1) and
acyl-CoA synthetase (EC 6.2.1.8) are ligases that synthesize p(4)A from AT
P and P-3 and, to a lesser extent. NpnN. T4 DNA ligase (EC 6.5.1.1) and T4
RNA ligase (EC 6.5.1.3) catalyze the synthesis of NpnN through the formatio
n of an E-AMP complex with liberation of pyrophosphate. DNA is an inhibitor
of the synthesis of NpnN and conversely, P-3 or nucleoside triphosphates i
nhibit the ligation of a single-strand break in duplex DNA catalyzed by T4
DNA ligase, which could have therapeutic implications. The synthesis of Npn
N catalyzed by T4 RNA ligase is inhibited by nucleoside 3'(2'),5'-bisphosph
ates. Reverse transcriptase (EC 2.7.7.49) although not a ligase, catalyzes,
as reported by others, the synthesis of Np(n)ddN in the process of removin
g a chain termination residue at the 3'-OH end of a growing DNA chain. (C)
2000 Elsevier Science Inc. All rights reserved.