Abstract
Analogs of pyrazinamide (=pyrazine-2-carboxamide; PZA), an essential component of short-course antituberculous chemotherapy, such as 5-chloropyrazinamide (5-Cl-PZA) act as competitive inhibitors of NADPH binding to purified mycobacterial fatty acid synthase I (FAS I) as shown by Saturation Transfer Difference (STD) NMR studies. In addition, pyrazinoic acid esters (POE) and 5-Cl-POE reversibly bind to FAS I with the relatively greater affinity of longer-chain esters for FAS I, clear from the STD amplification factors. The competitive binding of PZA and 5-Cl-PZA clearly illustrates that both agents bind FAS. In contrast to PZA, at low NADPH concentrations 5-Cl-PZA is a cooperative inhibitor of NADPH binding.
Original language | English (US) |
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Pages (from-to) | 2582-2596 |
Number of pages | 15 |
Journal | Chemistry and Biodiversity |
Volume | 9 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2012 |
Keywords
- Antituberculous activity
- Enzyme inhibition
- Fatty acid synthase I (FAS I)
- NADPH
- Pyrazinamide
- Saturation Transfer Difference (STD) NMR
ASJC Scopus subject areas
- Bioengineering
- Biochemistry
- General Chemistry
- Molecular Medicine
- Molecular Biology