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Enzymatic Synthesis of Cytidine Diphosphate 3,6-Dideoxyhexoses
Journal article   Open access   Peer reviewed

Enzymatic Synthesis of Cytidine Diphosphate 3,6-Dideoxyhexoses

Peter A. Rubenstein and Jack L. Strominger
The Journal of biological chemistry, Vol.249(12), pp.3789-3796
06/25/1974
DOI: 10.1016/S0021-9258(19)42543-X
PMID: 4833746
url
https://doi.org/10.1016/S0021-9258(19)42543-XView
Published (Version of record) Open Access

Abstract

In this paper is described a method for the purification of CDP- d -glucose pyrophosphorylase from a rough mutant of Pasteurella pseudotuberculosis type V which yields an enzyme 50% pure with high specific activity. When this material is subjected to gel electrophoresis at pH 7.5, the activity can be identified with one of the two major bands on the gel. By means of Sephadex gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis studies, the enzyme was found to be a single subunit composed of a single polypeptide chain of molecular weight 110,000. Michaelis-Menten kinetics was observed for the four compounds utilized by the enzyme. Values of K m for each of the substrates are as follows: CTP, 0.11 m m ; glucose 1-phosphate, 0.11 m m ; CDP- d -glucose, 0.41 m m ; and Mg 2 -PP i , 0.43 m m . The enzyme requires a divalent cation for activity, cobalt being the most active in the direction of CDP-glucose synthesis and magnesium and cobalt in the direction of pyrophosphorolysis. The enzyme was inhibited by CDP-ascarylose, CDP-abequose, and a mixture of CDP- d -fucose and CDP-6-deoxy- d -glucose. The inhibition by CDP-ascarylose is characterized by nonlinear Dixon plots of 1/ v versus I , a Hill plot with a slope of 2.3 for I , but linear Lineweaver-Burk plots for CTP and glucose 1-phosphate in the presence of the inhibitor. The presence of CDP-ascarylose causes a 10-fold increase in the K m for CTP, but K m for glucose 1-phosphate remains unchanged. The possible implications of these results are discussed.

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