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Synergistic inhibition of adenylosuccinate synthetase by nitrate and GDP
Author(s) -
Markham George D.,
Reed George H.
Publication year - 1975
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(75)80089-5
Subject(s) - george (robot) , citation , library science , foundation (evidence) , chemistry , classics , gerontology , medicine , history , art history , computer science , archaeology
Adenylosuccinate synthetase (IMP: L-aspartate ligase (GDP), EC 6.3.4.4) occupies a central position in the biosynthesis of AMP and in purine nucleotide cycling [ 11. Because of the enzyme’s unique function in adenine nucleotide synthesis, regulation and inhibition of this enzyme are of potential significance in control of cellular proliferation. Recent studies have shown that the planar nitrate anion may mimic the hypothetical metaphosphate intermediate in enzyme catalyzed phosphoryl transfer reactions [2-51. In several cases there is a strong interaction between nitrate and abortive enzymesubstrate complexes which lack only the y-phosphoryl group of the nucleotide moiety to be catalytically functional. This type of nitrate interaction was observed for the ligase enzyme, formyltetrahydrofolate synthetase, where nitrate enhanced the binding affinities of MnADP and of tetrahydrofolate five fold in the abortive complex, enzyme-MnADP-H4 folateformate [ 51. This observation suggested the possibility for nitrate inhibition of other enzymes of the ligase class. The present paper reports the synergistic inhibition of adenylosuccinate synthetase by nitrate and GDP. The influence of nitrate and GDP on the inhibitory action of the antineoplastic agent, 6-mercaptopurine ribotide has also been investigated.