Cisplatin Inhibits Protein Splicing, Identifying Inteins as Therapeutic Targets in Mycobacteria

Strategic Insights -

A team of researchers from the University of Science and Technology of China has discovered that the anticancer drug cisplatin can inhibit protein splicing, suggesting that inteins could be viable targets for small molecule inhibition in mycobacteria. According to the study, mycobacteria, such as Mycobacterium tuberculosis, harbor three protein splicing elements called inteins, which are essential for the function of critical proteins. The researchers found that cisplatin potently inhibits the splicing activity of the intein present in the RecA recombinase of M. tuberculosis, with an IC(50) of ~2 M.

Key Takeaways:

  • The inteins in mycobacteria are potential targets for antimycobacterial agents, as they are essential for the function of critical proteins.
  • Cisplatin, an anticancer drug, potently inhibits the splicing activity of the intein present in the RecA recombinase of M. tuberculosis with an IC(50) of ~2 M.
  • The inhibition activity of cisplatin is highly structure-dependent, with cisplatin exhibiting the best inhibitory effect among related platinum(II) complexes.
  • Cisplatin is toxic to M. tuberculosis with a minimum inhibitory concentration of ~40 M.
  • Intein overexpression can mitigate the toxicity of cisplatin in mycobacteria.
  • The study identifies a novel active site inhibitor of inteins and validates inteins as viable targets for small molecule inhibition in mycobacteria.

Statistics:

  • IC(50) of ~2 M for cisplatin inhibition of intein splicing activity.
  • Minimum inhibitory concentration of ~40 M for cisplatin toxicity against M. tuberculosis.
  • Mycobacteria harbor three protein splicing elements called inteins, vital for the function of critical proteins.

Sources:

  • Zhang L, et al. (2011). Cisplatin inhibits protein splicing, suggesting inteins as therapeutic targets in mycobacteria. Journal of Biological Chemistry, 286(2), 1277-1282.
  • University of Science and Technology of China, Dept. of Chemistry, CAS Key Laboratory of Soft Matter Chemistry.