6-Deoxyerythronolide B Synthase 1 Is Specifically Acylated by a Diketide Intermediate at the β-Ketoacyl-Acyl Carrier Protein Synthase Domain of Module 2†

Biochemistry ◽  
1996 ◽  
Vol 35 (48) ◽  
pp. 15244-15248 ◽  
Author(s):  
Naohiro Tsukamoto ◽  
Jo-Anne Chuck ◽  
Guanglin Luo ◽  
Camilla M. Kao ◽  
Chaitan Khosla ◽  
...  
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Deoxyerythronolide B Synthase

scholarly journals Extender Unit and Acyl Carrier Protein Specificity of Ketosynthase Domains of the 6-Deoxyerythronolide B Synthase

2006 ◽  
Vol 128 (9) ◽  
pp. 3067-3074 ◽  
Author(s):  
Alice Y. Chen ◽  
Nathan A. Schnarr ◽  
Chu-Young Kim ◽  
David E. Cane ◽  
Chaitan Khosla
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Protein Specificity ◽  
Extender Unit ◽  
Deoxyerythronolide B Synthase

scholarly journals Probing the interactions of an acyl carrier protein domain from the 6-deoxyerythronolide B synthase

2011 ◽  
Vol 20 (7) ◽  
pp. 1244-1255 ◽  
Author(s):  
Louise K. Charkoudian ◽  
Corey W. Liu ◽  
Stefania Capone ◽  
Shiven Kapur ◽  
David E. Cane ◽  
...  
Keyword(s):  
Acyl Carrier Protein ◽  
Protein Domain ◽  
Carrier Protein ◽  
Deoxyerythronolide B Synthase

4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study

2020 ◽  
Vol 20 ◽  
Author(s):  
Katharigatta N. Venugopala ◽  
Christophe Tratrat ◽  
Melendhran Pillay ◽  
Pran Kishore Deb ◽  
Deepak Chopra ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acyl Carrier Protein ◽  
Phenyl Group ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Benzyl Ester ◽  
Multi Drug Resistance ◽  
Carrier Protein ◽  
Molecular Docking Study ◽  
Lipinski’S Rule

Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB). Materials and Methods: Herein, the screening of a total of eight symmetrical 1,4-dihydropyridine (1,4-DHP) derivatives (4a-4h) was carried out for whole-cell anti-TB activity against the susceptible H37Rv and MDR strains of MTB. Results and Discussion: Most of the compounds exhibited moderate to excellent activity against the susceptible H37Rv. Moreover, the most promising compound 4f (against H37Rv) having para-trifluoromethyl phenyl group at 4-position and bis para-methoxy benzyl ester group at 3- and 5-positions of 1,4-dihydropyridine pharmacophore, exhibited no toxicity, but demonstrated weak activity against MTB strains resistant to isoniazid and rifampicin. In light of the inhibitory profile of the title compounds, enoyl-acyl carrier protein reductase (InhA) appeared to be the appropriate molecular target. Docking study of these derivatives against InhA receptor revealed favorable binding interactions. Further, in silico predicted ADME properties of these compounds 4a-4h were found to be in the acceptable ranges including satisfactory Lipinski’s rule of five, thereby indicating their potential as drug-like molecules. Conclusion: In particular, the 1,4-DHP derivative 4f can be considered as an attractive lead molecule for further exploration and development of more potent anti-TB agents as InhA inhibitors.

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