Mechanism of Nucleotide-Dependent Allosteric Regulation in Escherichia coli Aspartate Transcarbamoylase.

ABSTRACT: Discovered nearly 70 years ago, the allosteric regulation of Escherichia coli aspartate transcarbamoylase (ATCase) is discussed in every biochemistry textbook. ATCase catalyzes the first step in pyrimidine biosynthesis. Despite extensive research, the mechanism by which this enzyme is regulated by pyrimidine and purine nucleotides has remained elusive. Here, we present a detailed analysis of E. coli ATCase using a combination of biochemical assays, small-angle X-ray scattering (SAXS), cryo-electron microscopy (cryo-EM), and X-ray crystallography, revealing the mechanism of allosteric communication between nucleotide-binding sites and active sites. We show how the pyrimidine pair, CTP and UTP, synergistically inhibit the enzyme by inducing a quaternary structure that enforces

SUBMITTER: Miller RC 

PROVIDER: S-EPMC11601545 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature