Aspartate Transcarbamoylase

Aspartate carbamoyltransferase (also known as aspartate transcarbamoylase or ATCase) catalyzes the first reaction of pyrimidine biosynthesis, the condensation of carbamoyl phosphate and aspartic acid to form N-carbamoylaspartate.

This enzyme consists of a catalytic domain and a regulatory domain.

The catalytic domain catalyzes the carbamoylation of aspartate.

The catalytically inert, regulatory dimer binds allosteric effectors, such as ATP and CTP.

CTP, the end product of the biosynthesis of pyrimidines, is a feeback inhibitor.

Both ATP and CTP bind at the same allosteric binding site(the residues which make up this site are shown in red). Since CTP inhibits the enzyme it is known as a negative heterotropic effector. Conversely, ATP (which activates the enzyme) is known as a positive heterotropic effector.

ATP is the end product of purine biosynthesis. Thus high levels of ATP indicate that the levels of purine vs pyrimidine are unbalanced, so ATP activates ATCase to begin the production of more pyrimidines.

When ATP binds, Ala 11, Ile 12, Lys 94, and Glu 90 move - resulting in an enlargement of the nucleotide binding site (these residues are shown in purple).

Also located in the regulatory domain is a zinc binding site. When zinc binds , it is bound by 4 cysteine residues. .

Tyr77 is believed to be important for communication between the zinc binding site and the allosteric binding site.

For more information, consult:
Stevens, Raymond, et al. (1990) Biochemistry 29:7691-7701.

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