Aspartate Transcarbamoylase (ATCase)

This is the beginning of a page about Aspartate Transcarbamoylase (ATCase).

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Structure

ATCase consists of two catalytic trimers and three regulatory dimers that are completely separable units. It has been documented that the subunits can even combine when mixed together, reconstituting the enzyme. The two catalytic trimers are arranged on top of each other, with three dimers of the regulatory chains combining them. Significant interactions between the regulatory dimers and catalytic trimers occur; such as catalytic trimer chains contacting structural domains in the regulatory unit that are stabilized by a zinc ion bound to four cysteine residues. ATCase is largely alpha helical with large changes in quaternary structure occurring (trimers move 12 Angstroms apart and rotate approximately 10 degrees) upon allosteric affecters binding.

Function

Aspartate Transcarbamoylase catalyzes the first step in the biosynthesis of pyrimidines ( specifically called N-carbamoyl-aspartate) which ultimately yield pyrimidine nucleotides such as CTP. The cell must precisely regulate the amount of CTP in the cell because making it can be energetically expensive. Therefore, the rate of reaction catalyzed by ATCase is fast at low [CTP] but slows as [CTP] increases. However, CTP is quite different than the active site of ATCase, so at high levels it effectively inhibits the enzyme by binding to an allosteric/regulatory site rather than the active site. ATCase is a textbook example of a molecule under allosteric regulation in which the binding of substrate to one active site in a molecule increases the likelihood that the enzyme will bind more substrate, a phenomena called cooperativity.

Mechanism

ATCase displays features of a concerted mechanism due to the fact that changes in the enzyme are "all or none". In Michaelis-Menten kinetics, ATCase's curve is sigmoidal exemplifying a union of the R (active) and T (tense) states. High concentrations of CTP shift the curve right towards the T state, whereas high concentrations of ATP shift the curve left towards the R state.

Structural highlights

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