Nitro analogs of substrates for adenylosuccinate synthetase and adenylosuccinate lyase.

Arch Biochem Biophys, 1983/8;225(1):157-63.

Porter DJ, Rudie NG, Bright HJ

PMID: 6351751

Impact factor: 4.114

Abstract
The reactivities of the nitro analogs of the substrates of adenylosuccinate synthetase and adenylosuccinate lyase, the enzymes which catalyze the penultimate and last step, respectively, in the pathway for AMP biosynthesis have been examined. Alanine-3-nitronate, an aspartate analog, was a substrate for the synthetase from Azotobacter vinelandii, having a kcat/Km which was approximately 30% that for aspartate. The product of this reaction was N6-(L-1-carboxy-2-nitroethyl)-AMP. Of nine other substrate analogs tested, only cysteine sulfinate (having 5.5% of the activity of aspartate) was reactive. These results demonstrate the strict requirement of the synthetase for a negatively charged substituent, with a carboxylate-like geometry, at the beta-carbon of the alpha-amino acid substrate. The lyase, purified to homogeneity from brewer's yeast by a new procedure, did not utilize N6-(L-1-carboxy-2-nitroethyl)-AMP as a substrate. However, the nitronate form of this analog was a good inhibitor of the lyase (Km/Ki = 28 when compared to adenylosuccinate), suggesting that it mimics a carbanionic intermediate in the reaction pathway. The avid binding of bromphenol blue by the lyase (Ki = 0.95 microM) was used for active site titrations and for displacement of the enzyme, in the purification protocol, from blue Sepharose.
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