AI Article Synopsis

  • The study focused on screening a variety of natural compounds to find antibiotics that target respiratory enzymes in Pseudomonas aeruginosa.
  • A specific compound called siccanin was identified as a strong inhibitor of succinate dehydrogenase, showing effectiveness against certain pathogenic fungi.
  • Siccanin demonstrated selectivity in inhibiting enzymes from various species, making it a promising candidate for developing new chemotherapeutic agents.

Article Abstract

To identify antibiotics targeting to respiratory enzymes, we carried out matrix screening of a structurally varied natural compound library with Pseudomonas aeruginosa membrane-bound respiratory enzymes. We identified a succinate dehydrogenase inhibitor, siccanin (IC(50), 0.9 microM), which is a potent antibiotic against some pathogenic fungi like Trichophyton mentagrophytes and inhibits their mitochondrial succinate dehydrogenase. We found that siccanin was effective against enzymes from P. aeruginosa, P. putida, rat and mouse mitochondria but ineffective or less effective against Escherichia coli, Corynebacterium glutamicum, and porcine mitochondria enzyme. Action mode was mixed-type for quinone-dependent activity and noncompetitive for succinate-dependent activity, indicating the proximity of the inhibitor-binding site to the quinone-binding site. Species-selective inhibition by siccanin is unique among succinate dehydrogenase inhibitors, and thus siccanin is a potential lead compound for new chemotherapeutics.

Download full-text PDF

Source
http://dx.doi.org/10.1093/jb/mvp085DOI Listing

Publication Analysis

Top Keywords

succinate dehydrogenase
16
dehydrogenase inhibitor
8
respiratory enzymes
8
siccanin
5
siccanin rediscovered
4
rediscovered species-selective
4
succinate
4
species-selective succinate
4
dehydrogenase
4
inhibitor identify
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!