Structural and biochemical insights into the inhibition of Mycobacterium tuberculosis cyclic dinucleotide phosphodiesterase by a sulfur-modified cyclic dinucleotide analog

Key Points

• The study aims to explore how a sulfur-modified cyclic dinucleotide analog affects the inhibition of phosphodiesterase in Mycobacterium tuberculosis.
• Biochemical assays to assess binding interactions
• Structural analysis of enzyme-inhibitor complexes
• Evaluation of catalytic activity changes
• ES-cAAMP binds to Mycobacterium tuberculosis CdnP with a unique horseshoe conformation
• Inhibition occurs by competing with the substrate
• CdnP's catalytic activity significantly decreases when bound to the analog