Question

You have just synthesized a new antibiotic effective at preventing E. coli growth in agar culture. Now speculate on the proposed mechanism for the newly synthesized antibiotic’s interaction with ATCase. Describe the two limiting possible mechanisms by indicating the involvement of specific subunits of ATCase:

1. Competitive inhibitor

2. Allosteric effector

Answer 1

Aspartate transcarbomylase of Escherichia coli (E. coli) in an enzymes which regulates the biosynthesis of pyrimidine by catalysing the reaction of L-aspartate and carbomoyl phosphate to generate N-carbomoyl-L-aspartate. A closer look into the 3-dimensional structure of ATCase reveals the presence of two domains-the binding domain and the regulatory domain. The regulatory domain further has two subdivisions-one that is Zn domain (involved in binding of Zn cofactor) and Al domain (involved in binding of the allosteric effectors). This domain is not only responsible for catalysing the metabolic pathway but also in controlling the rate of the catalysis in response to various cellular conditions.

succinic acid,  N‐(phosphanacetyl)‐L‐aspartic acid etc. can serve as competitive inhibitors by producing analogous transition states in comparison to the transition state involving L-aspartate, carbomoyl phosphate and ATCase. Moreover the end product of the biosynthetic pathway ie, cytidine triphosphate (CTP) also serves as an inhibitor of the ATCase cativity by binding to the subunit responsible for ATP binding thereby reducing the affibity of the enzyme for substrate affinity. Thus the new antibiotic synthesis possibly has subunit which is analogous to L-aspartate substrate or CTP for competitive binding to ATP binding site.