• Journal of Integrative Natural Science
• /
• v.4 no.4
• /
• pp.273-277
• /
• 2011

It's a threat for the public health that H1N1 (Influenza virus A) causes disease and transmits among humans. WHO (world health organization) declared that the infections caused by the new strain had reached pandemic proportions. The approved neuraminidase inhibitors (Zanamivir and Oseltamivir) and related investigative drug (BCX-1812) are potent, specific inhibitors of influenza A and B viruses. These drugs are highly effective to prevent influenza A and B infections. Early therapeutic use reduces illness duration and respiratory complications. Recently, we found one of the potent inhibitor of erystagallin A ($IC_{50}$ of 2.04 ${\mu}M$) for neuraminidase target, this inhibitor shows most similar structure to its natural substrate, sialic acid. Therefore, we chose 1l7f to get the receptor structure for docking study among many crystal structures. A docking study has been performed in Surflex-Dock module in SYBYL 8.1. In the present study, we attempt to compare the docking studies of pterocarpin and erystagallin A with neuraminidase receptor structure. In the previous report, the methoxy group of pterocarpin had H-bonding with Arg residues. The present docking results for erystagallin A showed the backbone of hydroxyl group shows significant H-bonding interactions with Arg152 and Arg292. The results showed that erystagallin A interacts more favorably with distinctive binding site rather than original active site. Therefore, we tried to reveal plausible binding mode and important amino acid for this inhibitor using docking and site id search calculations of Sybyl. The results obtained from this work may be utilized to design novel inhibitors for neuraminidase.

• Molecules and Cells
• /
• v.41 no.9
• /
• pp.842-852
• /
• 2018

Notch signaling is an evolutionarily conserved pathway and involves in the regulation of various cellular and developmental processes. Ligand binding releases the intracellular domain of Notch receptor (NICD), which interacts with DNA-bound CSL [CBF1/Su(H)/Lag-1] to activate transcription of target genes. In the absence of NICD binding, CSL down-regulates target gene expression through the recruitment of various corepressor proteins including SMRT/NCoR (silencing mediator of retinoid and thyroid receptors/nuclear receptor corepressor), SHARP (SMRT/HDAC1-associated repressor protein), and KyoT2. Structural and functional studies revealed the molecular basis of these interactions, in which NICD coactivator and corepressor proteins competitively bind to ${\beta}-trefoil$ domain (BTD) of CSL using a conserved ${\varphi}W{\varphi}P$ motif (${\varphi}$ denotes any hydrophobic residues). To date, there are conflicting ideas regarding the molecular mechanism of SMRT-mediated repression of CSL as to whether CSL-SMRT interaction is direct or indirect (via the bridge factor SHARP). To solve this issue, we mapped the CSL-binding region of SMRT and employed a 'one- plus two-hybrid system' to obtain CSL interaction-defective mutants for this region. We identified the CSL-interaction module of SMRT (CIMS; amino acid 1816-1846) as the molecular determinant of its direct interaction with CSL. Notably, CIMS contains a canonical ${\varphi}W{\varphi}P$ sequence (APIWRP, amino acids 1832-1837) and directly interacts with CSL-BTD in a mode similar to other BTD-binding corepressors. Finally, we showed that CSL-interaction motif, rather than SHARP-interaction motif, of SMRT is involved in transcriptional repression of NICD in a cell-based assay. These results strongly suggest that SMRT participates in CSL-mediated repression via direct binding to CSL.

• Journal of the Korean Chemical Society
• /
• v.39 no.6
• /
• pp.453-458
• /
• 1995

We have applied Pb2+ to the structural analysis of 5S rRNA from Pseudomonas alcaligenes. The mode of Pb2+-induced clevage on 5S rRNA has shown several specific features which may be utilized for the examination of tertiary structure of 5S rRNA: Pb2+ does not attack the stable helical stems; single stranded regions or bulges are attacked in variable susceptibilities depending on the positions of the sequences or the bases on the molecule; unstable helical region d is not attacked at all; only 3' sided strand of unstable helical stem C is weakly attacked, leaving 5' sided strand unattacked. Based on the Pb2+ cleavage properties and the structural analysis of Xanthomonas celebensis 5S rRNA, we have proposed a working hypothesis for the tertiary interactions in 5S rRNA.

• Journal of Plant Biology
• /
• v.36 no.2
• /
• pp.127-132
• /
• 1993

Self-incompatibility in Brassica campestris is controlled by multi-allele system in a single genetic locus, the S locus, and it is elucidated that S-glycoproteins are S gene products. In this experiments, we examined the genetic mode(pollen tube behavior and segregation of S-glycoprotein), characteristic of S-glycoproteins and DNA constitution within nuclear genome on S gene family that unexplained by single locus model, and investigated the segregation pattern of S-glycoproteins in bred F1 generation. By diallel cross among the 15 plants within one family the existence of three types of homozygotes and three types of heterozygotes were observed, and segregation of S-allele could not explained by single locus model. From the results of IEF-immunoblot analysis for non-segregated individual plant, the segregation pattern of S specific bands was corresponded with results of diallel cross except with one case(SaSa genotype). The molecular weight of 6 different S-genotype varied in near by 50 kD, and each genotype expressed with 2 or 3 bands. Specific bands in SaSa, SbSb, ScSc has almost similar molecular weight between them. Southern analysis of genomic DNA probed with S-glycoprotein cDNA for 6 different genotypes revealed that there are clear difference in polymorphism, multiple bands of hybridization, when restriction enzymes of EcoR I were used. It could be assumed that there are several sequences related to the S-glycoprotein structural genes within their nuclear genome. Therefore, we suggested the possibilities that S-allele system could be controlled by multi-locus, that dominance-recessive interactions could be explained by modifier gene or supressor gene based on the results of abnormal segregation of S-glycoprotein in bred F1. The F2 analyses are progressing in now.

• Bulletin of the Korean Chemical Society
• /
• v.28 no.6
• /
• pp.947-952
• /
• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• Molecules and Cells
• /
• v.39 no.4
• /
• pp.316-321
• /
• 2016

The receptor activator of nuclear factor ${\kappa}B$ (RANK) and its ligand RANKL are key regulators of osteoclastogenesis and well-recognized targets in developing treatments for bone disorders associated with excessive bone resorption, such as osteoporosis. Our previous work on the structure of the RANK-RANKL complex revealed that Loop3 of RANK, specifically the non-canonical disulfide bond at the tip, performs a crucial role in specific recognition of RANKL. It also demonstrated that peptide mimics of Loop3 were capable of interfering with the function of RANKL in osteoclastogenesis. Here, we reported the structure-based design of a smaller peptide with enhanced inhibitory efficiency. The kinetic analysis and osteoclast differentiation assay showed that in addition to the sharp turn induced by the disulfide bond, two consecutive arginine residues were also important for binding to RANKL and inhibiting osteoclastogenesis. Docking and molecular dynamics simulations proposed the binding mode of the peptide to the RANKL trimer, showing that the arginine residues provide electrostatic interactions with RANKL and contribute to stabilizing the complex. These findings provided useful information for the rational design of therapeutics for bone diseases associated with RANK/RANKL function.

• The Proceeding of the Korean Institute of Electromagnetic Engineering and Science
• /
• v.6 no.1
• /
• pp.37-47
• /
• 1995

In this paper, the slot coupled stacked microstrip antenna, which has wide bandwidth characteristics because of the double tuning effects from the interactions between two patches and feeding slot and improves distortions of radiation patterns due to spurious radiation from feeder, is analyzed. For the analy- sis Green function in the spectrum domain and Galerkin method is applied with an accurate analysis mode for slot coupled feeding structure using the scattering analysis method. The basis functions are 3 EB modes for patches and 5 PWS modes for feeder. The slot coupled stacked microstrip antennas are designed and fabricated with the center frequency of 11.5 Ghz and 12.0 GHz. The experimental results show the wide bandwidth characteristics of 1.9 ~ 2.2 GHz and agree well with the simulation results which have 15~20% bandwidth.

• Tribology and Lubricants
• /
• v.22 no.2
• /
• pp.59-65
• /
• 2006

In hard disk drives as the head to disk spacing continues to decrease to facilitate recording densities, slider disk interactions have become much more severe due to direct contact of head and disk surfaces in both start/stop and flying cases. The slider disk interaction in CSS (contact-start-stop) mode is an important source of particle generation and tribocharge build-up. The tribocharge build-up in the slider disk interface can cause ESD (electrostatic discharge) damage. In turn, ESD can cause severe melting damage to MR or GMR heads. The spindle speed of typical hard disk drives has increased in recent years from 5400 rpm to 15000 rpm and even higher speeds are anticipated in the near future. And the increasing disk velocity leads to increasing disk acceleration and this might affect the tribocharging phenomena of the slider/disk interface. We investigated the tribocurrent/voltage build-up generated in HDD, operating at increasing disk accelerations. In addition, we examined the effects with relative humidity conditions and rest time. We found that the tribocurrent/voltage was generated during pico-slider/disk interaction and its level was about $3\sim16pA$ and $0.1\sim0.3V$, respectively. Tribocurrent/voltage build-up was reduced with increasing disk acceleration. Higher humidity conditions $(75\sim80%)$ produced lower levels tribovoltage/current. Therefore, a higher tribocharge is expected at a lower disk acceleration and lower relative humidity condition. Rest time affected the charge build-up at the slider-disk interface. The degree of tribocharge build-up increased with increasing rest time.

• Mass Spectrometry Letters
• /
• v.5 no.3
• /
• pp.84-88
• /
• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

• Coupled systems mechanics
• /
• v.2 no.3
• /
• pp.231-253
• /
• 2013

The impact of spar-nacelle-blade coupling on edgewise dynamic responses of spar-type floating wind turbines (S-FOWT) is investigated in this paper. Currently, this coupling is not considered explicitly by researchers. First of all, a coupled model of edgewise vibration of the S-FOWT considering the aerodynamic properties of the blade, variable mass and stiffness per unit length, gravity, the interactions among the blades, nacelle, spar and mooring system, the hydrodynamic effects, the restoring moment and the buoyancy force is proposed. The aerodynamic loads are combined of a steady wind (including the wind shear) and turbulence. Each blade is modeled as a cantilever beam vibrating in its fundamental mode. The mooring cables are modeled using an extended quasi-static method. The hydrodynamic effects calculated by using Morison's equation and strip theory consist of added mass, fluid inertia and viscous drag forces. The random sea state is simulated by superimposing a number of linear regular waves. The model shows that the vibration of the blades, nacelle, tower, and spar are coupled in all degrees of freedom and in all inertial, dissipative and elastic components. An uncoupled model of the S-FOWT is then formulated in which the blades and the nacelle are not coupled with the spar vibration. A 5MW S-FOWT is analyzed by using the two proposed models. In the no-wave sea, the coupling is found to contribute to spar responses only. When the wave loading is considered, the coupling is significant for the responses of both the nacelle and the spar.