• Journal of Microbiology and Biotechnology
• /
• v.21 no.10
• /
• pp.1097-1100
• /
• 2011

A toxin produced by Pseudomonas tolaasii, tolaasin, causes brown blotch disease in mushrooms. Tolaasin forms pores on the cellular membrane and destroys cell structure. Inhibiting the ability of tolaasin to form ion channels may be an effective method to protect against attack by tolaasin. However, it is first necessary to elucidate the three-dimensional structure of the ion channels formed by tolaasin. In this study, the structure of the tolaasin ion channel was determined in silico based on data obtained from nuclear magnetic resonance experiments.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.2
• /
• pp.455-458
• /
• 2011

In previous report, with the aid of receptor-oriented pharmacophore-based in silico screening, we characterized three novel hPNMT inhibitors (YPN010, YPN016, and YPN017) and proposed that the hydrogen bonding interaction between inhibitors and side chain of Lys57 is very important to inhibitory activity of hPNMT. To confirm the importance of Lys57, mutant with substitution of Lys57 with Ala was cloned and binding study was performed for a K57A mutant of hPNMT using STD-NMR and fluorescence experiments. The binding constants for three novel inhibitors with mutant hPNMT were dramatically decreased compared to those with wild-type protein. K57A mutant-induced conversion of noradrenaline to adrenaline was suppressed about 95 % compared to wild-type hPNMT. Mutagenic analysis using a K57A mutant confirmed the importance of the Lys57 residue in binding of the inhibitor candidate to hPNMT as well as enzymatic activity of hPNMT, implying that these results are consistent with our binding model.

• Genomics & Informatics
• /
• v.13 no.2
• /
• pp.60-67
• /
• 2015

The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

• Proceedings of the Korean Society of Life Science Conference
• /
• 2005.09a
• /
• pp.89-89
• /
• 2005

• Bulletin of the Korean Chemical Society
• /
• v.29 no.8
• /
• pp.1479-1484
• /
• 2008

Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

• Genomics & Informatics
• /
• v.20 no.4
• /
• pp.41.1-41.9
• /
• 2022

The pathogen Gallibacterium anatis has caused heavy economic losses for commercial poultry farms around the world. However, despite its importance, the functions of its hypothetical proteins (HPs) have been poorly characterized. The present study analyzed the functions and structures of HPs obtained from Gallibacterium anatis (NCTC11413) using various bioinformatics tools. Initially, all the functions of HPs were predicted using the VICMpred tool, and the physicochemical properties of the identified virulence proteins were then analyzed using Expasy's ProtParam server. A virulence protein (WP_013745346.1) that can act as a potential drug target was further analyzed for its secondary structure, followed by homology modeling and three-dimensional (3D) structure determination using the Swiss-Model and Phyre2 servers. The quality assessment and validation of the 3D model were conducted using ERRAT, Verify3D, and PROCHECK programs. The functional and phylogenetic analysis was conducted using ProFunc, STRING, KEGG servers, and MEGA software. The bioinformatics analysis revealed 201 HPs related to cellular processes (n = 119), metabolism (n = 61), virulence (n = 11), and information/storage molecules (n = 10). Among the virulence proteins, three were detected as drug targets and six as vaccine targets. The characterized virulence protein WP_013745346.1 is proven to be stable, a drug target, and an enzyme related to the citrate cycle in the present pathogen. This enzyme was also found to facilitate other metabolic pathways, the biosynthesis of secondary metabolites, and the biosynthesis of amino acids.

• Reproductive and Developmental Biology
• /
• v.34 no.3
• /
• pp.153-159
• /
• 2010

The 34 potently pig pheromonal odorants (1-32, 5755 & 7113) through structure-based virtual screening and ligand-based virtual screening method were selected and their ADMET and pharmacokinetics characters were evaluated and discussed quantitatively. The pheromonal odorants were projected on the following pre-calculated models, Caco-2 cell permeability, blood-brain barrier permeation, hERG inhibition and volume-distribution. From the results of in silico study, it is found that an optimal compound (31) either penetrating or have a little ($P_{caco2}$=-8.143) for Caco-2 cell permeability, moderate penetrating ability ($P_{BBB}$=0.082) for blood-brain barrier permeation, the low QT prolongation ($P_{hERG}$=1.137) for the hERG $K^+$ channel inhibition, and low distribution into tissues ($P_{VD}$=-5.468) for volume-distribution. Therefore, it is predicted that the compound (31) a topical application may be preferable from these based foundings.

• Bulletin of the Korean Chemical Society
• /
• v.30 no.8
• /
• pp.1835-1838
• /
• 2009

Inhibition of human phenylethanolamine N-methyltransferase (hPNMT) has been proposed as a method for the treatment of several mental processes which related on adrenaline metabolism. We performed in silico screening to identify flavonoid inhibitors of hPNMT using automated docking method and selected 9 inhibitor candidates based on ligand score (LigScore) and binding free energy (${\Delta}G_{bind}$) estimation. Among 9 flavonoid candidates, 7 flavonoids belong to flavones while the rest of them belong to flavanone. All candidates have common chemical features; two hydrogen bond interactions with side chain of Lys75 and backbone carbonyl oxygen of Asn39, and two hydrophobic interactions. One hydrophobic site is formed by Val53, Leu262, and Met258 and the other is made up of Phe182, Ala186, Tyr222, and Val269. This study can be helpful to understand the structural features for inhibition of PNMT and showed flavonoids as promising inhibitor candidates for hPNMT.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.4
• /
• pp.571-582
• /
• 2020

Quorum sensing (QS)-mediated infections cause severe diseases in human beings. The control of infectious diseases by inhibiting QS using antipathogenic drugs is a promising approach as antibiotics are proving inefficient in treating these diseases. Marine fungal (Pestalotiopsis sydowiana PPR) extract was found to possess effective antipathogenic characteristics. The minimum inhibitory concentration (MIC) of the fungal extract against test pathogen Pseudomonas aeruginosa PAO1 was 1,000 ㎍/ml. Sub-MIC concentrations (250 and 500 ㎍/ml) of fungal extract reduced QS-regulated virulence phenotypes such as the production of pyocyanin, chitinase, protease, elastase, and staphylolytic activity in P. aeruginosa PAO1 by 84.15%, 73.15%, 67.37%, 62.37%, and 33.65%, respectively. Moreover, it also reduced the production of exopolysaccharides (74.99%), rhamnolipids (68.01%), and alginate (54.98%), and inhibited the biofilm formation of the bacteria by 90.54%. In silico analysis revealed that the metabolite of P. sydowiana PPR binds to the bacterial QS receptor proteins (LasR and RhlR) similar to their respective natural signaling molecules. Cyclo(-Leu-Pro) (CLP) and 4-Hydroxyphenylacetamide (4-HPA) were identified as potent bioactive compounds among the metabolites of P. sydowiana PPR using in silico approaches. The MIC values of CLP and 4-HPA against P. aeruginosa PAO1 were determined as 250 and 125 ㎍/ml, respectively. All the antivirulence assays were conducted at sub-MIC concentrations of CLP (125 ㎍/ml) and 4-HPA (62.5 ㎍/ml), which resulted in marked reduction in all the investigated virulence factors. This was further supported by gene expression studies. The findings suggest that the metabolites of P. sydowiana PPR can be employed as promising QS inhibitors that target pathogenic bacteria.

• Journal of Korean Society of Environmental Engineers
• /
• v.28 no.10
• /
• pp.1055-1064
• /
• 2006

Extremely slow growing anammox(anaerobic ammonium oxidation) bacteria were cultivated using a combination of UASB(Upflow Anaerobic Sludge Blanket) reactor seeded with anaerobic granular sludge and carbon-fiber cultivating reactor. After 180 days of continuous cultivation, average nitrogen removal rate showed 0.54 kg $N/m^3-day$ when 0.6 kg $N/m^3-day$ of nitrogen loading was applied. The black granule was changed to brown and red granule as continuous operation, and the red granule was highly dependant on the high anammox activity. Microbial community structure of red granule in the UASB reactor was analyzed by molecular methods such as gene cloning, phylogenetic tree analysis, and FISH(Fluorescence In Situ Hybridization) method. As a result of gene cloning and phylogenetic tree analysis, 5 kinds of phylum were found to be Planctomycetes, Proteobacteria, Acidobacteria, Chlorobi and Chloroflexi. 13 clones were matched to anammox bacteria among 51 clones in the red anammox granule. In-silico test which used cloning information and FISH probe of the AMX368 was conducted to detect the presence of anammox bacteria in the red anammox granule. As a result of in-silico test only one clone was exactly matched to AMX368 but 11 clones was mutated one base among 18 bases representing all 12 clones are anammox bacteria. A filamentous Chloroflexi might be related to the granulation of anammox bacteria. As a result of FISH analysis, anammox bacteria was abundant in the red anammox granule.