Escherichia Coli Aspartate Transcarbamylase: The Relationship Between Structure and Function

  • Evan R. Kantrowitz
  • William N. Lipscomb
Part of the NATO ASI Series book series (NSSA, volume 183)


Aspartate transcarbamylase of Escherichia coli [EC] is a member of a special class of enzymes that not only catalyzes a cellular reaction but also controls the rate of a metabolic pathway. The enzymes in this class are usually large, each composed of more than one polypeptide chain, and catalyze a reaction at or near the beginning of a metabolic pathway. Aspartate transcarbamylase catalyzes the condensation of carbamyl phosphate with L-aspartate to produce N-carbamyl-L-aspartate and inorganic phosphate (Jones et al, 1955; Reichard & Hanshoff, 1956). This reaction is particularly important because once carbamylaspartate is formed it is committed to the biosynthesis of pyrimidines, a necessary component for nucleic acid biosynthesis. Aspartate transcarbamylase controls the rate of pyrimidine biosynthesis by altering its catalytic velocity in response to cellular levels of both pyrimidines and purines. The end product of the pyrimidine pathway, CTP, induces a decrease in catalytic velocity while, ATP, the end product of the parallel purine pathway, exerts the opposite effect, stimulating the catalytic activity (Yates & Pardee, 1956; Gerhart and Pardee, 1962 & 1963). In part, the relative amounts of purines and pyrimidines in the cell are thereby kept in balance for nucleic acid synthesis. By using X-ray crystallography and site-directed mutagenesis we have begun to delineate on the molecular level how this complex enzyme catalyzes the formation of carbamylaspartate and how it alters its catalytic activity in response to cellular metabolites.


Catalytic Subunit Allosteric Transition Domain Closure Carbamyl Phosphate Aspartate Transcarbamylase 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Evan R. Kantrowitz
    • 1
  • William N. Lipscomb
    • 2
  1. 1.Department of ChemistryBoston CollegeChestnut HillUSA
  2. 2.Gibbs LaboratoryHarvard UniversityCambridgeUSA

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