Docking studies of flavonoid compounds as inhibitors of β-ketoacyl acyl carrier protein synthase I (Kas I) of Escherichia coli.
Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), traveler's diarrhea and other clinical infections such as neonatal meningitis and pneumonia. The fatty acid biosynthesis is essential for the bacterial viability and growth. There are three types of β-ketoacyl acyl carrier protein synthase (KAS) which are important for overcoming the bacterial resistance problem. β-ketoacyl acyl carrier protein synthase I (KAS I) is member of the condensing enzyme family, which is a key catalyst in bacterial fatty acid biosynthesis, and thus an attractive target for novel antibioticsis related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. In this report, we performed docking study of E. coli (KAS I) and 50 flavonoids. Out of these 50 flavonoids, there are two compounds, genistein and isorhamnetin, that showed the superior binding energy while fully satisfying the conditions of drug likeliness. The predicted binding energy of genistein and isorhamnetin toward KAS I are -135.76kcal/mol and -132.42kcal/mol, respectively. These energies favorably compare to the biding energy of known drugs thiolactomicin and cerulenin that are -90.26kcal/mol and -99.64kcal/mol, respectively. The method used was docking with the selected E. coli (KAS I-PDB ID-1FJ4) using iGemdock. This was also found to obey the Lipinski's guidelines of five and to show the drug likeliness and bioavailability.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Aleppo, Aleppo University Street, Aleppo, Syria.
Ghalia
G
Sabbagh
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Aleppo, Aleppo University Street, Aleppo, Syria.
Noura
N
Berakdar
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020816:Amino Acid Motifs; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002569:Cerulenin / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry* / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D019833:Genistein / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013876:Thiophenes / Q000737:chemistry; D014584:User-Computer Interface
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D007527:Isoenzymes; D013876:Thiophenes; C047368:3-methylquercetin; D002569:Cerulenin; C035068:thiolactomycin; D011794:Quercetin; D019833:Genistein; C078182:beta-ketoacyl-acyl carrier protein synthase I; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
Docking; E. coli; FAS; Flavonoid; KAS I; iGemdock