• Bulletin of the Korean Chemical Society
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• v.27 no.4
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• pp.508-514
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• 2006

In this study, we have performed ab initio computer simulations to investigate the conformational and complexation characteristics of the trimethyl ether of p-tert-butylmonodeoxycalix[4]arene (6) with a potassium ion. The structures of different conformers of 6 and their potassium complexes were optimized by using ab initio RHF/6-31G and B3LYP/6-31G(d,p) methods. The relative stability of the various conformers of the uncomplexed 6 is in following order: cone (most stable) > 1-partial-cone ~ 2i-partial-cone > 2-partial-cone ~ 1,3-alternate > 3i-partial-cone. However, the relative stability of the conformational complexes of 6 with $K^+$ is in the following order: 2-partial cone ~ 1,3-alternate > cone > 3-partial cone > 1-partial cone (least stable). The highest binding strengths of 2-partial-cone and 1,3-alternate complexes originate from two strong cation-$\pi$ interactions and two strong cation-oxygen interactions in the complex of 6+$K^+$. Due to the cation-$\pi$ interactions, the calculated C-C bond distances in the arenes of the $K^+$-complexes are about 0.0048 $\AA$ longer than the values of their isolated hosts.

• Journal of Animal Science and Technology
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• v.59 no.9
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• pp.20.1-20.9
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• 2017

Background: Ribonuclease (RNase) is one of the few toxic proteins that are present constantly in snake venoms of all types. However, to date this RNase is still poorly studied in comparison not only with other toxic proteins of snake venom, but also with the enzymes of RNase group. The objective of this paper was to investigate some properties of RNase from venom of Vietnam cobra Naja atra. Methods: Kinetic methods and gel filtration chromatography were used to investigate RNase from venom of Vietnam cobra. Results: RNase from venom of Vietnam cobra Naja atra has some characteristic properties. This RNase is a thermostable enzyme and has high conformational stability. This is the only acidic enzyme of the RNase A superfamily exhibiting a high catalytic activity in the pH range of 1-4, with $pH_{opt}=2.58{\pm}0.35$. Its activity is considerably reduced with increasing ionic strength of reaction mixture. Venom proteins are separated by gel filtration into four peaks with ribonucleolytic activity, which is abnormally distributed among the isoforms: only a small part of the RNase activity is present in fractions of proteins with molecular weights of 12-15 kDa and more than 30 kDa, but most of the enzyme activity is detected in fractions of polypeptides, having molecular weights of less than 9 kDa, that is unexpected. Conclusions: RNase from the venom of Vietnam cobra is a unique member of RNase A superfamily according to its acidic optimum pH ($pH_{opt}=2.58{\pm}0.35$) and extremely low molecular weights of its major isoforms (approximately 8.95 kDa for RNase III and 5.93 kDa for RNase IV).

• BMB Reports
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• v.50 no.6
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• pp.329-334
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• 2017

Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2. Phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) at Tyr-705, a crucial site for STAT3 activation and target site of PTPN2, decreased upon exposure to the inhibitor. Our results suggest that PTP inhibitor XIX might be considered as an effective regulator of PTPN2 for treating diseases related to PTPN2.

• Journal of the Korean Chemical Society
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• v.53 no.6
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• pp.640-652
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• 2009

We have performed mPW1PW91 calculations to investigate the conformational characteristics and hydrogen bonds of p-tert-butylcalix[4]arene (1), p-tert-butylcalix[5]arene (2), calix[6]arene (3) and p-tertbutylcalix[6]arene (4). The structures of the different conformers of 1-3 were optimized by using mPW1PW91/6-31+G(d,p) method. The relative stability of the four conformers of 1 is in the following order: cone (most stable) > partial-cone > 1,2-alternate > 1,3-alternate. The relative stability of the conformers of 2 is in the following order: cone (most stable) > 1,2-alternate > partial-cone > 1,3-alternate. The relative stability of the various conformers of 3 is in the following order: cone (pinched: most stable) > partial-cone > cone (winged) - 1,2-alternate - 1,2,3-alternate > 1,4-alternate > 1,3-alternate > 1,3,5-alternate. The structures of the various conformers of 4 were optimized by using the mPW1PW91/6-31G(d,p) method followed by single point calculation of mPW1PW91/6-31+G(d,p). The relative stability of the conformers of 4 is in the following order: cone (pinched) > 1,2-alternate > cone (winged) > 1,4-alternate - partial-cone > 1,2,3-alternate > 1,3,5-alternate > 1,3-alternate. The primary factor affecting the relative stabilities of the various conformers of the 1-4 are the number and strength of the intramolecular hydrogen bonds. The hydrogen-bond distances are discussed based on two different calculation methods (B3LYP and mPW1PW91).

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1500-1506
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• 2011

Tyrosinase is a widespread enzyme with great promising capabilities. The Lineweaver-Burk plots of the catecholase reactions showed that the kinetics of mushroom tyrosinase (MT), activated by $Co^{2+}$ and $Zn^{2+}$ at different pHs (6, 7, 8 and 9) obeyed the non-essential activation mode. The binding of metal ions to the enzyme increases the maximum velocity of the enzyme due to an increase in the enzyme catalytic constant ($k_{cat}$). From the kinetic analysis, dissociation constants of the activator from the enzyme-metal ion complex ($K_a$) were obtained as $5{\times}10^4M^{-1}$ and $8.33{\times}10^3M^{-1}$ for $Co^{2+}$ and $Zn^{2+}$ at pH 9 and 6 respectively. The structural analysis of MT through circular dichroism (CD) and intensive fluorescence spectra revealed that the conformational stability of the enzyme in these pHs reaches its maximum value in the presence of each of the two metal ions.

• BMB Reports
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• v.33 no.3
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• pp.268-275
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• 2000

In contrast to the pyrimidine (6-4)pyrimidone photoproduct [(6-4) adduct], its Dewar valence isomer (Dewar product) is low mutagenic and produces a broad range of mutations with a 42 % replicating error frequency. In order to determine the origin of the mutagenic property of the Dewar product, we used experimental NMR restraints and molecular dynamics to determine the solution structure of a Dewar·lesion DNA decamer duplex, which contains a mismatched base pair between the 3'-T residue and an opposed G residue. The 3'-T of the Dewar lesion forms stable hydrogen bonds with the opposite G residue. The helical bending and unwinding angles of the DW/GA duplex, however, are much higher than those of the DW/AA duplex. The stable hydrogen bonding of the G 15 residue does not increase the thermal stability of the overall helix. It also does not restore the distorted backbone conformation of the DNA helix that is caused by the forming of a Dewar lesion. These structural features implicate that no thermal stability, or conformational benefits of G over A opposite the 3'-T of the Dewar lesion, facilitate the preferential incorporation of an A. This is in accordance with the A rule during translesion replication and leads to the low frequent $3'-T{\rightarrow}C$ mutation at this site.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1505-1509
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• 2008

Comparative molecular simulations were performed to establish molecular interaction and inhibitory effect of flavonoid myricetin on formation of amyloid fibris. For computational comparison, the conformational stability of myricetin with amyloid $\beta$ -peptide (A$\beta$ ) and $\beta$ -amyloid fibrils (fA$\beta$) were traced with multiple molecular dynamics simulations (MD) using the CHARMM program from Monte Carlo docked structures. Simulations showed that the inhibition by myricetin involves binding of the flavonoid to fA$\beta$ rather than A$\beta$ . Even in MD simulations over 5 ns at 300 K, myricetin/fA$\beta$ complex remained stable in compact conformation for multiple trajectories. In contrast, myricetin/A$\beta$ complex mostly turned into the dissociated conformation during the MD simulations at 300 K. These multiple MD simulations provide a theoretical basis for the higher inhibitory effect of myricetin on fibrillogenesis of fA$\beta$ relative to A$\beta$ . Significant binding between myricetin and fA$\beta$ observed from the computational simulations clearly reflects the previous experimental results in which only fA$\beta$ had bound to the myricetin molecules.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.75-75
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• 2003

We report here the results on N-acetyl-N'-dimethylamide of proline (Ac-Pro-NM $e_2$) calculated using the ab initio molecular orbital method with the self-consistent reaction field (SCRF) theory at the HF level with the 6-31+G(d) basis set to investigate the conformational preference of polyproline depending on the cis/trans peptide bonds and down/up puckerings along the backbone torsion angle $\square$ in the gas phase, chloroform, and water. In the gas phase, Ac-Pro-NM $e_2$ has seven local minima of tFd, tFu, cFd, cFu, cAu, tAu, and cAd conformations. In particular, polyproline conformations tFd, tFu, cFd, and cFu are found to be more stable than $\square$-helical conformations cAu, tAu, and cAd. In contrast, Ac-Pro-NHMe has seven local minima of tCd, tCu, cBd, cAu, tAu, cFd, and cFu conformations. Conformations tCd and tCu are found to be most stable, which is ascribed to the intramolecular hydrogen bond between C=O of acetyl group and $N^{~}$ H of N'-methyl amide group. The stability of the cFd conformation (i.e., the polyproline I structure) in chloroform is somewhat increased, relative to that in water, although tFd and tFu conformations (i.e., the polyproline II structure) are dominate both in chloroform and water. The population of backbone conformations feasible in chloroform and water is consistent with the experiments. This work is supported by a Korea Research Foundation Grant (KRF-2002-041-C00129).

• Bulletin of the Korean Chemical Society
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• v.31 no.6
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• pp.1479-1484
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• 2010

Photosynthesis uses light energy to drive the oxidation of water at an oxygen-evolving catalytic site within photosystem II (PSII). Chlorophyll binding by the photosystem II subunit S protein, PsbS, was found to be necessary for energy-dependent quenching (qE), the major energy-dependent component of non-photochemical quenching (NPQ) in Arabidopsis thaliana. It is proposed that PsbS acts as a trigger of the conformational change that leads to the establishment of nonphotochemical quenching. However, the exact structure and function of PsbS in PSII are still unknown. Here, we clone and express the recombinant PsbS gene from Arabidopsis thaliana in E. coli and purify the resulting homogeneous protein. We used various biochemical and biophysical techniques to elucidate PsbS structure and function, including circular dichroism (CD), fluorescence, and DSC. The protein shows optimal stability at $4^{\circ}C$ and pH 7.5. The CD spectra of PsbS show that the conformational changes of the protein were strongly dependent on pH conditions. The CD curve for PsbS at pH 10.5 curve had the deepest negative peak and the peak of PsbS at pH 4.5 was the least negative. The fluorescence emission spectrum of the purified PsbS protein was also measured, and the ${\lambda}_{max}$ was found to be at 328 nm. PsbS revealed some structural changes under varying temperature and oxygen gas condition.

• BMB Reports
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• v.35 no.2
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• pp.155-164
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• 2002

The structural aspects of ervatamin B have been studied in different types of alcohol. This alcohol did not affect the structure or activity of ervatamin B under neutral conditions. At a low pH (3.0), different kinds of alcohol have different effects. Interestingly, at a certain concentration of non-fluorinated, aliphatic, monohydric alcohol, a conformational switch from the predominantly $\alpha$-helical to $\beta$-sheeted state is observed with a complete loss of tertiary structure and proteolytic activity. This is contrary to the observation that alcohol induces mostly the $\alpha$helical structure in proteins. The O-state of ervatamin B in 50% methanol at pH 3.0 has enhanced the stability towards GuHCl denaturation and shows a biphasic transition. This suggests the presence of two structural parts with different stabilities that unfold in steps. The thermal unfolding of ervatamin B in the O-state is also biphasic, which confirms the presence of two domains in the enzyme structure that unfold sequentially. The differential stabilization of the structural parts may also be a reflection of the differential stabilization of local conformations in methanol. Thermal unfolding of ervatamin B in the absence of alcohol is cooperative, both at neutral and low pH, and can be fitted to a two state model. However, at pH 2.0 the calorimetric profiles show two peaks, which indicates the presence of two structural domains in the enzyme with different thermal stabilities that are denatured more or less independently. With an increase in pH to 3.0 and 4.0, the shape of the DSC profiles change, and the two peaks converge to a predominant single peak. However, the ratio of van't Hoff enthalpy to calorimetric enthalpy is approximated to 2.0, indicating non-cooperativity in thermal unfolding.