Jul 21, 1992

Ionization of amino acid residues involved in the catalytic mechanism of aspartate transcarbamoylase

Biochemistry
J L TurnbullH K Schachman

Abstract

The chemical and kinetic mechanisms of the reaction catalyzed by the catalytic trimer of aspartate transcarbamoylase have been examined. The variation of the kinetic parameters with pH indicated that at least four ionizing amino acid residues are involved in substrate binding and catalysis. The pH dependence of K(ia) for carbamoyl phosphate and the K(i) for N-(phosphonoacetyl)-L- aspartate revealed that a protonated residue with a pK value of 9.0 is required for the binding of carbamoyl phosphate. However, the variation with pH of K(i) for succinate, a competitive inhibitor of aspartate, and for cysteine sulfinate, a slow substrate, showed that a single residue with a pK value of 7.3 must be protonated for binding these analogues and, by inference, aspartate. The profile of log V against pH displayed a decrease in reaction rate at low and high pH, suggesting that two groups associated with the Michaelis complex, a deprotonated residue with a pK value of 7.2 and a protonated group with a pK value of 9.5, are involved in catalysis. By contrast, the catalytically productive form of the enzyme-carbamoyl phosphate complex, as illustrated in the bell-shaped pH dependence of log (V/K)(asp), is one in which a residue with a pK value of...Continue Reading

Mentioned in this Paper

Cysteine sulfinate
Alkalescens-Dispar Group
Aspartic Acid, Magnesium-Potassium (2:1:2) Salt
Aspartate
Proteins, Recombinant DNA
Succinates
Ions
Carbon Radioisotopes
Carbamoyltransferases
NSC 224131, tetrasodium salt

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