The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform

Yong-doo Park - One of the best experts on this subject based on the ideXlab platform.

  • Effects of L-Malic Acid on Alpha-Glucosidase: Inhibition Kinetics and Computational Molecular Dynamics Simulations
    Applied biochemistry and biotechnology, 2014
    Co-Authors: Lin Gou, Yong-doo Park, Jinhyuk Lee, Hai-meng Zhou, Yi Zhan, Xi-yao Wang, Jun-mo Yang
    Abstract:

    The inhibitory effect of L-malic acid (MA) on alpha-glucosidase (EC 3.2.1.20) was investigated by combination study between Inhibition Kinetics and computational simulations. The results from the serial Kinetics demonstrated that MA could directly inactivate the enzyme activity in a dose-dependent manner and a typical non-competitive type, as well as in a fast inactivate process without detectable time course. The tertiary conformation study with an application of spectrofluorimetry showed that MA modulated the tertiary structural conformation of alpha-glucosidase both on the overall and on regional active site pocket, which monitored by red-shift intrinsic fluorescence peak with decreases intensities, and the significant intensity increasing of 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence, respectively. To have more insight, we also adapted the computational molecular dynamics (MD) simulations. The results showed that MA was located in the entrance of active pocket for the catalytic reaction and blocked the passage of substrate. It confirmed that MA inhibits as a non-competitive type, not direct docking to the glucose binding site. Our study provides important molecular mechanisms to figure out alpha-glucosidase Inhibition that might associate to development of type 2 diabetes mellitus drug.

  • Effect of Ca2+ on the activity and structure of α-glucosidase: Inhibition Kinetics and molecular dynamics simulations
    Journal of bioscience and bioengineering, 2014
    Co-Authors: Xin Zhang, Yong-doo Park, Shi Long, Qing Sheng, Ling Yao, Dong Shen, Hai-meng Zhou, Jinhyuk Lee
    Abstract:

    Understanding the mechanism of Inhibition of α-glucosidase (EC 3.2.1.20) is clinically important because of the involvement of this enzyme in type 2 diabetes mellitus. In this study, we conducted Inhibition Kinetics of α-glucosidase with Ca2+ and 10-ns molecular dynamics simulations. We found that direct binding of Ca2+ to the enzyme induced structural changes and inhibited enzyme activity. Ca2+ inhibited α-glucosidase in a mixed-type reaction (Ki = 27.0 ± 2.0 mM) and directly induced the unfolding of α-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca2+ ions may interact with α-glucosidase residues and that the Ca2+ binding sites are associated with the structural changes in α-glucosidase. Our study provides insight into the mechanism of the Ca2+-induced structural changes in α-glucosidase and the Inhibition of ligand binding. These results suggest that Ca2+ could act as a potent inhibitor of α-glucosidase for the treatment of type 2 diabetes mellitus.

  • The effect of fucoidan on tyrosinase: computational molecular dynamics integrating Inhibition Kinetics
    Journal of biomolecular structure & dynamics, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Jun-mo Yang, Yong-doo Park, Jinhyuk Lee, Guo-ying Qian
    Abstract:

    Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. In this study, we investigated the inhibitory effect of fucoidan on tyrosinase via a combination of Inhibition Kinetics and computational simulations. Fucoidan reversibly inhibited tyrosinase in a mixed-type manner. Time-interval Kinetics showed that the Inhibition was processed as first order with biphasic processes. For further insight, we simulated dockings with various sizes of molecular models (monomer to decamer) of fucoidan and showed that the best binding energy change results were obtained from the pentamer (−1.89 kcal/mol) and the hexamer (−1.97 kcal/mol) models of AutoDock Vina. The molecular dynamics simulation confirmed the binding mechanisms between tyrosinase and fucoidan and suggested that fucoidan mostly interacts with several residues including copper ions located in the active site. Our study suggests that fucoidan might be a potential natural antipigment agent.

  • effect of hesperetin on tyrosinase Inhibition Kinetics integrated computational simulation study
    International Journal of Biological Macromolecules, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Li Yan, Jun-mo Yang, Guo-ying Qian, Yong-doo Park, Sufang Wang
    Abstract:

    Abstract Tyrosinase inhibitors have potential applications in medicine, cosmetics and agriculture to prevent hyperpigmentation or browning effects. Some of the flavonoids mostly found in herbal plants and fruits are revealed as tyrosinase inhibitors. We studied the inhibitory effects of one such flavonoid, hesperetin, on mushroom tyrosinase using Inhibition Kinetics and computational simulation. Hesperetin reversibly inhibited tyrosinase in a competitive manner with K i  = 4.03 ± 0.26 mM. Measurements of ANS-binding fluorescence showed that hesperetin induced the hydrophobic disruption of tyrosinase. For further insight, we used the docking algorithms to simulate binding between tyrosinase and hesperetin. Simulation was successful (binding energies for Dock6.3: −34.41 kcal/mol and for AutoDock4.2: −5.67 kcal/mol) and showed that a copper ion coordinating with 3 histidine residues (HIS61, HIS85, and HIS259) within the active site pocket was chelated via hesperetin binding. Our study provides insight into the Inhibition of tyrosinase in response to flavonoids. A combination of Inhibition Kinetics and computational prediction may facilitate the identification of potential natural tyrosinase inhibitors such as flavonoids and the prediction of their inhibitory mechanisms.

  • The effects of acrylamide on brain creatine kinase: Inhibition Kinetics and computational docking simulation.
    International journal of biological macromolecules, 2008
    Co-Authors: He-chang Zou, Daeui Park, Yong-doo Park, Long Shi, Seong Jin Park, Jong Bhak, Fei Zou
    Abstract:

    The occurrence of acrylamide is frequently observed in processed foods. Therefore, the harmful effects of acrylamide on metabolic enzymes are important to understand. We studied the inhibitory effects of acrylamide on the brain creatine kinase (CK-BB). We found that CK-BB was kinetically inactivated by acrylamide accompanied by the disruption of the hydrophobic surface. Acrylamide mainly interacted with the thiol (-SH) residue of CK-BB and resulted in alkylation. A computational docking simulation supported that acrylamide directly bound to the active site of CK-BB where cysteine and glycine residues interacted mainly. The Inhibition Kinetics combined with computational prediction can be useful in order to have insights into the mechanisms regarding environmentally hazardous factors at the molecular level.

Jun-mo Yang - One of the best experts on this subject based on the ideXlab platform.

  • Effects of L-Malic Acid on Alpha-Glucosidase: Inhibition Kinetics and Computational Molecular Dynamics Simulations
    Applied biochemistry and biotechnology, 2014
    Co-Authors: Lin Gou, Yong-doo Park, Jinhyuk Lee, Hai-meng Zhou, Yi Zhan, Xi-yao Wang, Jun-mo Yang
    Abstract:

    The inhibitory effect of L-malic acid (MA) on alpha-glucosidase (EC 3.2.1.20) was investigated by combination study between Inhibition Kinetics and computational simulations. The results from the serial Kinetics demonstrated that MA could directly inactivate the enzyme activity in a dose-dependent manner and a typical non-competitive type, as well as in a fast inactivate process without detectable time course. The tertiary conformation study with an application of spectrofluorimetry showed that MA modulated the tertiary structural conformation of alpha-glucosidase both on the overall and on regional active site pocket, which monitored by red-shift intrinsic fluorescence peak with decreases intensities, and the significant intensity increasing of 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence, respectively. To have more insight, we also adapted the computational molecular dynamics (MD) simulations. The results showed that MA was located in the entrance of active pocket for the catalytic reaction and blocked the passage of substrate. It confirmed that MA inhibits as a non-competitive type, not direct docking to the glucose binding site. Our study provides important molecular mechanisms to figure out alpha-glucosidase Inhibition that might associate to development of type 2 diabetes mellitus drug.

  • The effect of fucoidan on tyrosinase: computational molecular dynamics integrating Inhibition Kinetics
    Journal of biomolecular structure & dynamics, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Jun-mo Yang, Yong-doo Park, Jinhyuk Lee, Guo-ying Qian
    Abstract:

    Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. In this study, we investigated the inhibitory effect of fucoidan on tyrosinase via a combination of Inhibition Kinetics and computational simulations. Fucoidan reversibly inhibited tyrosinase in a mixed-type manner. Time-interval Kinetics showed that the Inhibition was processed as first order with biphasic processes. For further insight, we simulated dockings with various sizes of molecular models (monomer to decamer) of fucoidan and showed that the best binding energy change results were obtained from the pentamer (−1.89 kcal/mol) and the hexamer (−1.97 kcal/mol) models of AutoDock Vina. The molecular dynamics simulation confirmed the binding mechanisms between tyrosinase and fucoidan and suggested that fucoidan mostly interacts with several residues including copper ions located in the active site. Our study suggests that fucoidan might be a potential natural antipigment agent.

  • Effects of isorhamnetin on tyrosinase: Inhibition Kinetics and computational simulation.
    Bioscience biotechnology and biochemistry, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Jun-mo Yang, Hyoung Oh Jeong, Guo-ying Qian
    Abstract:

    We studied the inhibitory effects of isorhamnetin on mushroom tyrosinase by Inhibition Kinetics and computational simulation. Isorhamnetin reversibly inhibited tyrosinase in a mixed-type manner at K i=0.235 ± 0.013 mM. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate(ANS)-binding fluorescence showed that isorhamnetin did not induce significant changes in the tertiary structure of tyrosinase. To gain insight into the inactivation process, the Kinetics were computed via time-interval measurements and continuous substrate reactions. The results indicated that inactivation induced by isorhamnetin was a first-order reaction with biphasic processes. To gain further insight, we simulated docking between tyrosinase and isorhamnetin. Simulation was successful (binding energies for Dock6.3: −32.58 kcal/mol, for AutoDock4.2: −5.66 kcal/mol, and for Fred2.2: −48.86 kcal/mol), suggesting that isorhamnetin interacts with several residues, such as HIS244 and MET280. This strategy of predicting tyrosinase i...

  • effect of hesperetin on tyrosinase Inhibition Kinetics integrated computational simulation study
    International Journal of Biological Macromolecules, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Li Yan, Jun-mo Yang, Guo-ying Qian, Yong-doo Park, Sufang Wang
    Abstract:

    Abstract Tyrosinase inhibitors have potential applications in medicine, cosmetics and agriculture to prevent hyperpigmentation or browning effects. Some of the flavonoids mostly found in herbal plants and fruits are revealed as tyrosinase inhibitors. We studied the inhibitory effects of one such flavonoid, hesperetin, on mushroom tyrosinase using Inhibition Kinetics and computational simulation. Hesperetin reversibly inhibited tyrosinase in a competitive manner with K i  = 4.03 ± 0.26 mM. Measurements of ANS-binding fluorescence showed that hesperetin induced the hydrophobic disruption of tyrosinase. For further insight, we used the docking algorithms to simulate binding between tyrosinase and hesperetin. Simulation was successful (binding energies for Dock6.3: −34.41 kcal/mol and for AutoDock4.2: −5.67 kcal/mol) and showed that a copper ion coordinating with 3 histidine residues (HIS61, HIS85, and HIS259) within the active site pocket was chelated via hesperetin binding. Our study provides insight into the Inhibition of tyrosinase in response to flavonoids. A combination of Inhibition Kinetics and computational prediction may facilitate the identification of potential natural tyrosinase inhibitors such as flavonoids and the prediction of their inhibitory mechanisms.

  • TXM13 human melanoma cells: a novel source for the Inhibition Kinetics of human tyrosinase and for screening whitening agents.
    Biochemistry and cell biology = Biochimie et biologie cellulaire, 2006
    Co-Authors: Yong-doo Park, So Yeon Kim, You-jeong Lyou, Dong-youn Lee, Jun-mo Yang
    Abstract:

    Research involving whitening agents requires several steps of experimentation, and the initial step is to test whitening agents with human melanocytes and those with human tyrosinase. Unfortunately, it takes a long time to gather human melanocytes, and these cells have some limitations when it comes to performing experiments, such as their passage difficulties and their cost. In this study, we suggest that the TXM13 human melanoma cells could be a useful cell candidate for studying human tyrosinase Inhibition and depigmentation. We applied a tyrosinase inhibitor, such as dithioglycerine (DTGC), to validate the cell line's usefulness, and we tested the effect of DTGC on TXM13 melanogenesis. The results showed that human tyrosinase from TXM13 was appropriate, according to the Inhibition Kinetics, and that the conspicuous depigmentation of TXM13 occurred after DTGC treatment without downregulating the tyrosinase expression level. When taken together, our findings provide useful information regarding the use of the TXM13 melanoma cells for the development of whitening agents.

Heiko Rühl - One of the best experts on this subject based on the ideXlab platform.

  • Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics
    International journal of molecular sciences, 2021
    Co-Authors: Sara Reda, Jens Müller, Anna Pavlova, Behnaz Pezeshkpoor, Johannes Oldenburg, Bernd Pötzsch, Heiko Rühl
    Abstract:

    Inactivation of thrombin by the endogenous inhibitor antithrombin (AT) is a central mechanism in the regulation of hemostasis. This makes hereditary AT deficiency, which is caused by SERPINC1 gene mutations, a major thrombophilic risk factor. Aim of this study was to assess to what extent AT mutations impair thrombin Inhibition Kinetics. The study population included 36 thrombophilic patients with 19 different mutations and mean AT levels of 65% in a thrombin-based functional assay, and 26 healthy controls. To assess thrombin Inhibition Kinetics, thrombin (3.94 mU/mL final concentration) was added to citrated plasma. Subsequently, endogenous thrombin Inhibition was stopped by addition of the reversible thrombin inhibitor argatroban and the amount of argatroban-complexed thrombin quantified using an oligonucleotide-based enzyme capture assay. The plasma half-life of human thrombin was significantly longer in patients with AT mutations than in the controls (119.9 versus 55.9 s). Moreover, it was disproportionately prolonged when compared with preparations of wild type AT in plasma, in whom a comparable thrombin half-life of 120.8 s was reached at a distinctly lower AT level of 20%. These findings may help to better understand the increased thrombotic risk of SERPINC1 mutations with near normal AT plasma levels in functional assays.

Daeui Park - One of the best experts on this subject based on the ideXlab platform.

  • Effects of isorhamnetin on tyrosinase: Inhibition Kinetics and computational simulation.
    Bioscience biotechnology and biochemistry, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Jun-mo Yang, Hyoung Oh Jeong, Guo-ying Qian
    Abstract:

    We studied the inhibitory effects of isorhamnetin on mushroom tyrosinase by Inhibition Kinetics and computational simulation. Isorhamnetin reversibly inhibited tyrosinase in a mixed-type manner at K i=0.235 ± 0.013 mM. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate(ANS)-binding fluorescence showed that isorhamnetin did not induce significant changes in the tertiary structure of tyrosinase. To gain insight into the inactivation process, the Kinetics were computed via time-interval measurements and continuous substrate reactions. The results indicated that inactivation induced by isorhamnetin was a first-order reaction with biphasic processes. To gain further insight, we simulated docking between tyrosinase and isorhamnetin. Simulation was successful (binding energies for Dock6.3: −32.58 kcal/mol, for AutoDock4.2: −5.66 kcal/mol, and for Fred2.2: −48.86 kcal/mol), suggesting that isorhamnetin interacts with several residues, such as HIS244 and MET280. This strategy of predicting tyrosinase i...

  • effect of hesperetin on tyrosinase Inhibition Kinetics integrated computational simulation study
    International Journal of Biological Macromolecules, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Li Yan, Jun-mo Yang, Guo-ying Qian, Yong-doo Park, Sufang Wang
    Abstract:

    Abstract Tyrosinase inhibitors have potential applications in medicine, cosmetics and agriculture to prevent hyperpigmentation or browning effects. Some of the flavonoids mostly found in herbal plants and fruits are revealed as tyrosinase inhibitors. We studied the inhibitory effects of one such flavonoid, hesperetin, on mushroom tyrosinase using Inhibition Kinetics and computational simulation. Hesperetin reversibly inhibited tyrosinase in a competitive manner with K i  = 4.03 ± 0.26 mM. Measurements of ANS-binding fluorescence showed that hesperetin induced the hydrophobic disruption of tyrosinase. For further insight, we used the docking algorithms to simulate binding between tyrosinase and hesperetin. Simulation was successful (binding energies for Dock6.3: −34.41 kcal/mol and for AutoDock4.2: −5.67 kcal/mol) and showed that a copper ion coordinating with 3 histidine residues (HIS61, HIS85, and HIS259) within the active site pocket was chelated via hesperetin binding. Our study provides insight into the Inhibition of tyrosinase in response to flavonoids. A combination of Inhibition Kinetics and computational prediction may facilitate the identification of potential natural tyrosinase inhibitors such as flavonoids and the prediction of their inhibitory mechanisms.

  • The effects of acrylamide on brain creatine kinase: Inhibition Kinetics and computational docking simulation.
    International journal of biological macromolecules, 2008
    Co-Authors: He-chang Zou, Daeui Park, Yong-doo Park, Long Shi, Seong Jin Park, Jong Bhak, Fei Zou
    Abstract:

    The occurrence of acrylamide is frequently observed in processed foods. Therefore, the harmful effects of acrylamide on metabolic enzymes are important to understand. We studied the inhibitory effects of acrylamide on the brain creatine kinase (CK-BB). We found that CK-BB was kinetically inactivated by acrylamide accompanied by the disruption of the hydrophobic surface. Acrylamide mainly interacted with the thiol (-SH) residue of CK-BB and resulted in alkylation. A computational docking simulation supported that acrylamide directly bound to the active site of CK-BB where cysteine and glycine residues interacted mainly. The Inhibition Kinetics combined with computational prediction can be useful in order to have insights into the mechanisms regarding environmentally hazardous factors at the molecular level.

  • The Effect of Histidine Residue Modification on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Prediction
    Journal of Biomolecular Structure and Dynamics, 2008
    Co-Authors: Lin Guo, Daeui Park, Yong-doo Park, Long Shi, Seong Jin Park, Jong Bhak, Zhen-long Ren, Fei Zou
    Abstract:

    We found that the histidine chemical modification of tyrosinase conspicuously inactivated enzyme activity. The substrate reactions with diethylpyridinecarbamate showed slow-binding Inhibition Kinetics (KI = 0.24 +/- 0.03 mM). Bromoacetate, as another histidine modifier, was also applied in order to study Inhibition Kinetics. The bromoacetate directly induced the exposures of hydrophobic surfaces following by complete inactivation via ligand binding. For further insights, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and diethylpyridinecarbamate. The docking simulation was shown to the significant binding energy scores (-3.77 kcal/mol by AutoDock4 and -25.26 kcal/mol by Dock6). The computational prediction was informative to elucidate the role of free histidine residues at the active site, which are related to substrate accessibility during tyrosinase catalysis.

Guo-ying Qian - One of the best experts on this subject based on the ideXlab platform.

  • The effect of fucoidan on tyrosinase: computational molecular dynamics integrating Inhibition Kinetics
    Journal of biomolecular structure & dynamics, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Jun-mo Yang, Yong-doo Park, Jinhyuk Lee, Guo-ying Qian
    Abstract:

    Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. In this study, we investigated the inhibitory effect of fucoidan on tyrosinase via a combination of Inhibition Kinetics and computational simulations. Fucoidan reversibly inhibited tyrosinase in a mixed-type manner. Time-interval Kinetics showed that the Inhibition was processed as first order with biphasic processes. For further insight, we simulated dockings with various sizes of molecular models (monomer to decamer) of fucoidan and showed that the best binding energy change results were obtained from the pentamer (−1.89 kcal/mol) and the hexamer (−1.97 kcal/mol) models of AutoDock Vina. The molecular dynamics simulation confirmed the binding mechanisms between tyrosinase and fucoidan and suggested that fucoidan mostly interacts with several residues including copper ions located in the active site. Our study suggests that fucoidan might be a potential natural antipigment agent.

  • Effects of isorhamnetin on tyrosinase: Inhibition Kinetics and computational simulation.
    Bioscience biotechnology and biochemistry, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Jun-mo Yang, Hyoung Oh Jeong, Guo-ying Qian
    Abstract:

    We studied the inhibitory effects of isorhamnetin on mushroom tyrosinase by Inhibition Kinetics and computational simulation. Isorhamnetin reversibly inhibited tyrosinase in a mixed-type manner at K i=0.235 ± 0.013 mM. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate(ANS)-binding fluorescence showed that isorhamnetin did not induce significant changes in the tertiary structure of tyrosinase. To gain insight into the inactivation process, the Kinetics were computed via time-interval measurements and continuous substrate reactions. The results indicated that inactivation induced by isorhamnetin was a first-order reaction with biphasic processes. To gain further insight, we simulated docking between tyrosinase and isorhamnetin. Simulation was successful (binding energies for Dock6.3: −32.58 kcal/mol, for AutoDock4.2: −5.66 kcal/mol, and for Fred2.2: −48.86 kcal/mol), suggesting that isorhamnetin interacts with several residues, such as HIS244 and MET280. This strategy of predicting tyrosinase i...

  • effect of hesperetin on tyrosinase Inhibition Kinetics integrated computational simulation study
    International Journal of Biological Macromolecules, 2012
    Co-Authors: Zhi-jiang Wang, Shang-jun Yin, Daeui Park, Hae Young Chung, Li Yan, Jun-mo Yang, Guo-ying Qian, Yong-doo Park, Sufang Wang
    Abstract:

    Abstract Tyrosinase inhibitors have potential applications in medicine, cosmetics and agriculture to prevent hyperpigmentation or browning effects. Some of the flavonoids mostly found in herbal plants and fruits are revealed as tyrosinase inhibitors. We studied the inhibitory effects of one such flavonoid, hesperetin, on mushroom tyrosinase using Inhibition Kinetics and computational simulation. Hesperetin reversibly inhibited tyrosinase in a competitive manner with K i  = 4.03 ± 0.26 mM. Measurements of ANS-binding fluorescence showed that hesperetin induced the hydrophobic disruption of tyrosinase. For further insight, we used the docking algorithms to simulate binding between tyrosinase and hesperetin. Simulation was successful (binding energies for Dock6.3: −34.41 kcal/mol and for AutoDock4.2: −5.67 kcal/mol) and showed that a copper ion coordinating with 3 histidine residues (HIS61, HIS85, and HIS259) within the active site pocket was chelated via hesperetin binding. Our study provides insight into the Inhibition of tyrosinase in response to flavonoids. A combination of Inhibition Kinetics and computational prediction may facilitate the identification of potential natural tyrosinase inhibitors such as flavonoids and the prediction of their inhibitory mechanisms.