Structure, Function, and Inhibition of Adenylosuccinate Lyase (ADSL) from <i>Mycobacterium tuberculosis</i>.

ABSTRACT: Adenylosuccinate lyase (ADSL), encoded by the purB gene, is an essential enzyme in the purine biosynthesis pathway of Mycobacterium tuberculosis (Mtb), making it a promising target for antimicrobial drug development. Here, we report the expression, purification, kinetic characterization, high-throughput screening (HTS), and structural analysis of Mtb ADSL. We developed a highly sensitive and scalable bioluminescent assay using a PPDK-luciferase coupling system to quantify ADSL enzymatic activity via AMP detection. This assay enabled reliable kinetic analysis and successful pilot HTS of a small-molecule library, identifying bithionol and tetraiodothyroacetic acid (Tetrac) as inhibitors of Mtb ADSL. Inhibitory activity was confirmed using an o

SUBMITTER: Singh V 

PROVIDER: S-EPMC12812255 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature