scholarly journals β-Hydroxyacyl-acyl Carrier Protein Dehydratase (FabZ) fromFrancisella tularensisandYersinia pestis: Structure Determination, Enzymatic Characterization, and Cross-Inhibition Studies

Biochemistry ◽  
2016 ◽  
Vol 55 (7) ◽  
pp. 1091-1099 ◽  
Author(s):  
Brian E. McGillick ◽  
Desigan Kumaran ◽  
Casey Vieni ◽  
Subramanyam Swaminathan
Keyword(s):  
Structure Determination ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Enzymatic Characterization ◽  
Inhibition Studies ◽  
Cross Inhibition

scholarly journals Expression of a recombinant, 4’-Phosphopantetheinylated, active M. tuberculosis Fatty acid Synthase I in E. coli

2018 ◽  
Author(s):  
Szilvia Baron ◽  
Yoav Peleg ◽  
Jacob Grunwald ◽  
David Morgenstern ◽  
Nadav Elad ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Drug Target ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Spectrophotometric Analysis ◽  
Carrier Protein ◽  
E Coli ◽  
Drug Inhibition ◽  
Nadph Oxidation ◽  
Inhibition Studies

AbstractFatty acid synthase 1 (FAS I) from Mycobacterium. tuberculosis (Mtb) is an essential protein and a promising drug target. FAS I is a multi-functional, multi-domain protein that is organized as a large (1.9 MDa) homohexameric complex. Acyl intermediates produced during fatty acid elongation are attached covalently to an acyl carrier protein (ACP) domain. This domain is activated by the transfer of a 4’-Phosphopantetheine (4’-PP, also termed P-pant) group from CoA to ACP catalyzed by a 4’-PP transferase, termed acyl carrier protein synthase (AcpS). In order to obtain an activated FAS I in E. coli, we transformed E. coli with tagged Mtb fas1 and acpS genes encoded by a separate plasmid.We induced the expression of Mtb FAS I following induction of AcpS expression. FAS I was purified by Strep-Tactin affinity chromatography. Activation of Mtb FAS I was confirmed by the identification of a bound P-pant group on serine at position 1808 by mass spectrometry. The purified FAS I displayed biochemical activity shown by spectrophotometric analysis of NADPH oxidation and by CoA production, using the Ellman reaction. The purified Mtb FAS I forms a hexameric complex shown by negative staining and cryo-EM. Purified hexameric and active Mtb FAS I is required for binding and drug inhibition studies and for structurefunction analysis of this enzyme. This relatively simple and short procedure for Mtb FAS I production should facilitate studies of this enzyme.

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.

scholarly journals Acyl Carrier Protein

1972 ◽  
Vol 247 (19) ◽  
pp. 6234-6242
Author(s):  
Daniel A.K. Roncari ◽  
Ralph A. Bradshaw ◽  
P. Roy Vagelos
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein
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