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Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC(50) of BA against jack-bean ure...

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Autores principales: Tan, Lirong, Su, Jiyan, Wu, Dianwei, Yu, Xiaodan, Su, Zuqing, He, Jingjin, Wu, Xiaoli, Kong, Songzhi, Lai, Xiaoping, Lin, Ji, Su, Ziren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807542/
https://www.ncbi.nlm.nih.gov/pubmed/24198731
http://dx.doi.org/10.1155/2013/879501
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author Tan, Lirong
Su, Jiyan
Wu, Dianwei
Yu, Xiaodan
Su, Zuqing
He, Jingjin
Wu, Xiaoli
Kong, Songzhi
Lai, Xiaoping
Lin, Ji
Su, Ziren
author_facet Tan, Lirong
Su, Jiyan
Wu, Dianwei
Yu, Xiaodan
Su, Zuqing
He, Jingjin
Wu, Xiaoli
Kong, Songzhi
Lai, Xiaoping
Lin, Ji
Su, Ziren
author_sort Tan, Lirong
collection PubMed
description Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC(50) of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of K (i) = 3.89 × 10(−3) mM was followed by a slow isomerization into the final complex with an overall inhibition constant of K (i)* = 1.47 × 10(−4) mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases.
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spelling pubmed-38075422013-11-06 Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin Tan, Lirong Su, Jiyan Wu, Dianwei Yu, Xiaodan Su, Zuqing He, Jingjin Wu, Xiaoli Kong, Songzhi Lai, Xiaoping Lin, Ji Su, Ziren ScientificWorldJournal Research Article Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC(50) of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of K (i) = 3.89 × 10(−3) mM was followed by a slow isomerization into the final complex with an overall inhibition constant of K (i)* = 1.47 × 10(−4) mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases. Hindawi Publishing Corporation 2013-10-01 /pmc/articles/PMC3807542/ /pubmed/24198731 http://dx.doi.org/10.1155/2013/879501 Text en Copyright © 2013 Lirong Tan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tan, Lirong
Su, Jiyan
Wu, Dianwei
Yu, Xiaodan
Su, Zuqing
He, Jingjin
Wu, Xiaoli
Kong, Songzhi
Lai, Xiaoping
Lin, Ji
Su, Ziren
Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin
title Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin
title_full Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin
title_fullStr Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin
title_full_unstemmed Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin
title_short Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin
title_sort kinetics and mechanism study of competitive inhibition of jack-bean urease by baicalin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807542/
https://www.ncbi.nlm.nih.gov/pubmed/24198731
http://dx.doi.org/10.1155/2013/879501
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