Abstract
Mycobacterium tuberculosis remains the leading cause of death by a bacterial pathogen worldwide. Increasing prevalence of multidrug-resistant organisms means prioritizing identification of targets for antituberculars. 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (HsaD), part of the cholesterol metabolism operon, is vital for survival within macrophage. The C-C bond hydrolase, HsaD, has a serine protease-like catalytic triad. We tested a range of serine protease and esterase inhibitors for their effects on HsaD activity. As well as providing a potential starting point for drug development, the data provides evidence for the mechanism of C-C bond hydrolysis. This screen also provides a route to initiate development of fragment-based inhibitors.
| Original language | English |
|---|---|
| Pages (from-to) | 42-47 |
| Number of pages | 6 |
| Journal | FEMS Microbiology Letters |
| Volume | 350 |
| Issue number | 1 |
| Early online date | 1 Jan 2014 |
| DOIs | |
| Publication status | Published - Jan 2014 |
Keywords
- Antitubercular Agents
- Cholinesterase Inhibitors
- Drug Design
- Fatty Acids, Unsaturated
- Hydrolases
- Hydrolysis
- Inhibitory Concentration 50
- Macrophages
- Microbial Viability
- Models, Molecular
- Mycobacterium tuberculosis
- Protein Conformation
- Pseudomonas
- Serine Proteinase Inhibitors
- Spectrometry, Mass, Electrospray Ionization
- Journal Article
Access to Document
- Full-text PDF (accepted author manuscript)
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/femsle/article/350/1/42/555894 . Please refer to any applicable terms of use of the publisher.
- Supplementary information PDF
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/femsle/article/350/1/42/555894 . Please refer to any applicable terms of use of the publisher.