The effect of thiobarbituric acid on tyrosinase: Inhibition kinetics and computational simulation

Shang Jun Yin; Yue Xiu Si; Zhi Jiang Wang; Su Fang Wang; Sangho Oh; Sanghyuk Lee; Seon Mi Sim; Jun Mo Yang; Guo Ying Qian; Jinhyuk Lee; Yong Doo Park

doi:10.1080/07391102.2011.10507398

The effect of thiobarbituric acid on tyrosinase: Inhibition kinetics and computational simulation

Shang Jun Yin, Yue Xiu Si, Zhi Jiang Wang, Su Fang Wang, Sangho Oh, Sanghyuk Lee, Seon Mi Sim, Jun Mo Yang, Guo Ying Qian, Jinhyuk Lee, Yong Doo Park

Department of Life Science

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Tyrosinase plays various roles in organisms and much research has focused on the regulation of tyrosinase activity. We studied the inhibitory effect of thiobarbituric acid (TBA) on tyro-sinase. Our kinetic study showed that TBA inhibited tyrosinase in a reversible noncompetitive manner (K _i = 14.0 ± 8.5 mM and IC₅₀ = 8.0 ± 1.0 mM). Intrinsic and ANS-binding fluorescences studies were also performed to gain more information regarding the binding mechanism. The results showed that no tertiary structural changes were obviously observed. For further insight, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and TBA. The docking simulation was successful with significant scores (binding energy for AutoDock4:—5.52 kcal/mol) and suggested that TBA was located in the active site. The 11 ns molecular dynamics simulation convinced that the four HIS residues (residue numbers: 57, 90, 250, and 282) were commonly responsible for the interaction with TBA. Our results provide a new inhibition strategy that works using an antioxidant rather than targeting the copper ions within the tyrosinase active site.

Original language	English
Pages (from-to)	463-470
Number of pages	8
Journal	Journal of Biomolecular Structure and Dynamics
Volume	29
Issue number	3
DOIs	https://doi.org/10.1080/07391102.2011.10507398
State	Published - Dec 2011

Bibliographical note

Funding Information:
This work was financially supported by the Natural Science Foundation of Ningbo City (2011A610019 and 2011A610039). Dr. Guo-Ying Qian was supported by Consultation Program funded by the Science and Technology Department of Zhe-jiang Province (2008C0200-2). Dr. Jun-Mo Yang was supported by the grant of the Korea Health 21 R&D Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea, 01-PJ3-PG6-01GN12-0001) and by a grant (Grant No. C-A9-220-1) from Samsung Biomedical Research Institute. Dr. Yong-Doo Park was supported by a grant from the project supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. Y2091212).

Keywords

Docking simulation
Inhibition kinetics
Thiobarbituric acid
Tyrosinase

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10.1080/07391102.2011.10507398

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title = "The effect of thiobarbituric acid on tyrosinase: Inhibition kinetics and computational simulation",

abstract = "Tyrosinase plays various roles in organisms and much research has focused on the regulation of tyrosinase activity. We studied the inhibitory effect of thiobarbituric acid (TBA) on tyro-sinase. Our kinetic study showed that TBA inhibited tyrosinase in a reversible noncompetitive manner (K i = 14.0 ± 8.5 mM and IC50 = 8.0 ± 1.0 mM). Intrinsic and ANS-binding fluorescences studies were also performed to gain more information regarding the binding mechanism. The results showed that no tertiary structural changes were obviously observed. For further insight, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and TBA. The docking simulation was successful with significant scores (binding energy for AutoDock4:—5.52 kcal/mol) and suggested that TBA was located in the active site. The 11 ns molecular dynamics simulation convinced that the four HIS residues (residue numbers: 57, 90, 250, and 282) were commonly responsible for the interaction with TBA. Our results provide a new inhibition strategy that works using an antioxidant rather than targeting the copper ions within the tyrosinase active site.",

keywords = "Docking simulation, Inhibition kinetics, Thiobarbituric acid, Tyrosinase",

author = "Yin, {Shang Jun} and Si, {Yue Xiu} and Wang, {Zhi Jiang} and Wang, {Su Fang} and Sangho Oh and Sanghyuk Lee and Sim, {Seon Mi} and Yang, {Jun Mo} and Qian, {Guo Ying} and Jinhyuk Lee and Park, {Yong Doo}",

note = "Funding Information: This work was financially supported by the Natural Science Foundation of Ningbo City (2011A610019 and 2011A610039). Dr. Guo-Ying Qian was supported by Consultation Program funded by the Science and Technology Department of Zhe-jiang Province (2008C0200-2). Dr. Jun-Mo Yang was supported by the grant of the Korea Health 21 R&D Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea, 01-PJ3-PG6-01GN12-0001) and by a grant (Grant No. C-A9-220-1) from Samsung Biomedical Research Institute. Dr. Yong-Doo Park was supported by a grant from the project supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. Y2091212).",

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AU - Yin, Shang Jun

AU - Si, Yue Xiu

AU - Wang, Zhi Jiang

AU - Wang, Su Fang

AU - Oh, Sangho

AU - Lee, Sanghyuk

AU - Sim, Seon Mi

AU - Yang, Jun Mo

AU - Qian, Guo Ying

AU - Lee, Jinhyuk

AU - Park, Yong Doo

N1 - Funding Information: This work was financially supported by the Natural Science Foundation of Ningbo City (2011A610019 and 2011A610039). Dr. Guo-Ying Qian was supported by Consultation Program funded by the Science and Technology Department of Zhe-jiang Province (2008C0200-2). Dr. Jun-Mo Yang was supported by the grant of the Korea Health 21 R&D Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea, 01-PJ3-PG6-01GN12-0001) and by a grant (Grant No. C-A9-220-1) from Samsung Biomedical Research Institute. Dr. Yong-Doo Park was supported by a grant from the project supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. Y2091212).

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N2 - Tyrosinase plays various roles in organisms and much research has focused on the regulation of tyrosinase activity. We studied the inhibitory effect of thiobarbituric acid (TBA) on tyro-sinase. Our kinetic study showed that TBA inhibited tyrosinase in a reversible noncompetitive manner (K i = 14.0 ± 8.5 mM and IC50 = 8.0 ± 1.0 mM). Intrinsic and ANS-binding fluorescences studies were also performed to gain more information regarding the binding mechanism. The results showed that no tertiary structural changes were obviously observed. For further insight, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and TBA. The docking simulation was successful with significant scores (binding energy for AutoDock4:—5.52 kcal/mol) and suggested that TBA was located in the active site. The 11 ns molecular dynamics simulation convinced that the four HIS residues (residue numbers: 57, 90, 250, and 282) were commonly responsible for the interaction with TBA. Our results provide a new inhibition strategy that works using an antioxidant rather than targeting the copper ions within the tyrosinase active site.

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KW - Inhibition kinetics

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SN - 0739-1102

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JF - Journal of Biomolecular Structure and Dynamics

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ER -

The effect of thiobarbituric acid on tyrosinase: Inhibition kinetics and computational simulation

Abstract

Bibliographical note

Keywords

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