PhD Fellow, ICGEB New Delhi Component, INDIA
Delineation of Molecular mechanism of Purine Metabolic Regulation in E. coli Adenine phosphoribosyltransferase (APRT)
Host: L. Banks
The salvage pathway of nucleotide synthesis ensures an energy-efficient supply of nucleotides, provide
adaptations to nutrient-starved conditions, and aid in antibiotic tolerance. Adenine phosphoribosyltransferase (APRT) catalyzes a reversible reaction converting adenine into adenosine monophosphate (AMP). In proteobacteria, a large class of human pathogenic bacteria, the mechanistic regulation of APRT remains underexplored. This study aims to decipher the regulation of purine metabolism by APRT in this class.
We determined atomic-resolution structures of the apo and substrate-bound (adenine, AMP) forms of E. coli APRT using X-ray crystallography, uncovering a novel adenine-binding mode distinct from those observed in other APRTs. How this newly discovered binding mode affects EcAPRT activity has been explored. We identified loop residues Glu103 and Tyr104 as crucial catalytic residues in enzyme activity assays. However, these residues are 14 Å away from the nucleobase ring in determined monosubstrate bound forms.
This research paves the way for applying protein molecular dynamics simulations and a scaffold-based cryo-EM approach to capture intermediate states in proteobacterial APRT activity. Targeting these states with inhibitors offers a promising strategy for antimicrobial interventions.
International Seminar Programme
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