Escherichia coli feedback inhibition

Aspartate transcarbamoylase (ATCase) from Escherichia coli is the most studied and best known regulatory enzyme. Yates and Pardee (1956) were the first to propose that the activity of ATCase is controlled by end product inhibition. This feedback inhibition was later studied in more detail by Gerhart and Pardee (1961, 1962, 1963). The three-dimensional structure of ATCase was determined by Lip-scombe and his coworkers [Wiley etal. (1971), Wiley and Lipscomb (1968), Warren etal. (1973)]. 

FIGURE 3.3 L-Phenylalanine-mediated feedback inhibition of wild-type Escherichia coli K12 prephenate dehydratase (JN302) and four feedback inhibition-resistant enzyme variants (JN305-JN308). Activity is expressed as a percentage of normal wild-type enzyme activity. 

Ogawa-Miyata Y, Kojima H, Sano K (2001) Mutation analysis of the feedback inhibition site of aspartokinase III of Escherichia coli K-12 and its use in L-threonine production. Biosci Biotech Biochem 65 1149-1154... 

In this experiment we will examine some of the properties of the aspartate transcarbamylase of Escherichia coli, which is typical of many enzymes subject to feedback inhibition and which has been studied extensively. Aspartate transcarbamylase (ATCase) catalyzes the first reaction unique to the biosynthesis of pyrimidine nucleotides. ATCase is subject to specific inhibition by quite low concentrations of one of its end products, cytidine 5 -triphosphate (CTP). This relationship and two other regulatory interactions important to the control of pyrimidine biosynthesis are summarized in Figure 9-1. 

Woolfolk, C. A. Stadtman, E. R. (1967). Regulation of glutamine synthetase III. Cumulative feedback inhibition of glutamine synthetase from Escherichia coli. Arch. Biochem. Biophys. 118,736-755. 

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