• Bulletin of the Korean Chemical Society
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• v.28 no.8
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• pp.1335-1340
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• 2007

β-Ketoacyl acyl carrier protein synthase (KAS) III is a particularly attractive target in the type II fatty acid synthetic pathway, since it is central to the initiation of fatty acid synthesis. Enterococcus faecalis, a Grampositive bacterium, is one of the major causes of hospital acquired infections. The rise of multidrug-resistant of most bacteria requires the development of new antibiotics, such as inhibition of the KAS III. In order to block the fatty acid synthesis by inhibition of KAS III, at first, three dimensional structure of Enterococcus faecalis KAS III (efKAS III) was determined by comparative homology modeling using MODELLER based on x-ray structure of Staphylococcus aureus KAS III (saKAS III) which is a gram-positive bacteria and is 36.1% identical in amino acid sequences with efKAS III. Since His-Asn-Cys catalytic triad is conserved in efKAS III and saKAS III, substrate specificity of efKAS III and saKAS III and the size of primer binding pocket of these two proteins are expected to be similar. Ligand docking study of efKAS III with naringenin and apigenin showed that naringenin docked more strongly with efKAS III than apigenin, resulting in the intensive hydrogen bond network between naringenin and efKAS III. Also, only naringenin showed antibacterial activity against E. faecalis at 256 μg/mL. This study may give practical implications of flavonoids for antimicrobial effects against E. faecalis.

• Bulletin of the Korean Chemical Society
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• v.32 no.9
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• pp.3219-3222
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• 2011

Three types of ${\beta}$-ketoacyl acyl carrier protein synthase (KAS) are important for overcoming the bacterial resistance problem. Recently, we reported the discovery of a antimicrobial flavonoid, YKAF01 (3,6-dihydroxyflavone), which exhibits antibacterial activity against Gram-positive bacteria through inhibition of ${\beta}$-ketoacyl acyl carrier protein synthase III (KAS III). In this report, we suggested that YKAF01 can be an inhibitor ${\beta}$-ketoacyl acyl carrier protein synthase I (KAS I) with dual inhibitory activity for KAS I as well as KAS III. KAS I is related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. We performed docking study of Escherichia coli KAS I (ecKAS I) and YKAF01, and determined their binding model. YKAF01 binds to KAS I with high binding affinity ($2.12{\times}10^6$) and exhibited an antimicrobial activity against the multidrug-resistant E. coli with minimal inhibitory concentration (MIC) value of 512 ${\mu}g$/mL. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2695-2699
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• 2011

${\beta}$ Ketoacyl acyl carrier protein synthase III (KAS III) initiates fatty acid synthesis in bacteria and is a key target enzyme to overcome the antibiotic resistance problem. In our previous study, we found flavonoid inhibitors of Enterococcus faecalis KAS III and proposed three potent antimicrobial flavonoids against Enterococcus faecalis and Vancomycin-resistant Enterococcus faecalis with MIC values in the range of 128-512 ${\mu}g/mL$ as well as high binding affinities on the order from $10^6$ to $10^7\;M^{-1}$. Using these series of flavonoids, we conducted biological assays as well as docking study to find potent flavonoids inhibitors of Staphylococcus aureus KAS III with specificities against Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. Here, we propose that naringenin (5,7,4'-trihydroxyflavanone) and eriodictyol (5,7,3',4'-tetrahydroxyflavanone) are potent antimicrobial inhibitors of Staphylococcus aureus KAS III with binding affinity of $3.35{\times}10^5$ and $2.01{\times}10^5\;M^{-1}$, respectively. Since Arg38 in efKAS III is replaced with Met36 in saKAS III, this key difference caused one hydrogen bond missing in saKAS III compared with efKAS III, resulting in slight discrepancy in their binding interactions as well as decrease in binding affinities. 4'-OH and 7-OH of these flavonoids participated in hydrogen bonding interactions with backbone carbonyl of Phe298 and Ser152, respectively. In particular, these flavonoids display potent antimicrobial activities against various MRSA strains in the range of 64 to 128 ${\mu}M$ with good binding affinities.

• The Bulletin of The Korean Astronomical Society
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• v.35 no.2
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• pp.75.1-75.1
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• 2010

The nature and origin of the intergalactic magnetic field (IGMF) are an outstanding problem of cosmology, yet they are not well understood. Measuring Faraday rotation (RM) is one of a few promising methods to explore the IGMF. We have theoretically investigated RM using a model of the IGMF based on a MHD turbulence dynamo (Ryu et al. 2008; Cho et al. 2009). In the previous KAS meeting, we reported the results for the present-day local universe; for instance, the probability distribution function (PDF) of ${\mid}RM{\mid}$ follows the lognormal distribution, the root mean square (rms) value for filaments is ~1 rad m^{-2}, and the power spectrum peaks at ~1 h^{-1} Mpc scale. In this talk, we extend our study of RM; by stacking simulation data up to redshift z=5 and taking account of the redshift distribution of radio sources, we have reproduced an observable view of RM through filaments against background radio sources. Our findings are as follows. The inducement of RM is a random walk process, so that the rms of RM increases with increasing path length. The rms value of RM for filaments reaches several rad m^{-2}. The PDF still follows the lognormal distribution, and the power spectrum of RM peaks at less than degree scale. Our predictions of RM could be tested, for instance, with LOFAR, ASKAP, MEERKAT, and SKA.