Inactivation of jack bean urease by scutellarin: Elucidation of inhibitory efficacy, kinetics and mechanism.

Abstract: In the present study, the inactivation effect of scutellarin (SL) on jack bean urease was investigated to elucidate the inhibitory potency, kinetics and mechanism of inhibition. It was revealed that SL acted as a concentration- and time-dependent inactivator of urease characteristic of slo...

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Publicado en:Fitoterapia Vol. 91; pp. 60 - 68
Autores principales: Wu, Dian-Wei, Yu, Xiao-Dan, Xie, Jian-Hui, Su, Zu-Qing, Su, Ji-Yan, Tan, Li-Rong, Huang, Xiao-Qi, Chen, Jian-Nan, Su, Zi-Ren
Formato: Journal Article
Publicado: Elsevier B.V. Dec2013
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Fitoterapia
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      dt: Dec2013
      vid: 91
      pid: 467
      pub: Elsevier B.V.
      place: New York, New York
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        10.1016/j.fitote.2013.08.012
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        atl: Inactivation of jack bean urease by scutellarin: Elucidation of inhibitory efficacy, kinetics and mechanism.
      aug:
        au:
          Wu, Dian-Wei
          Yu, Xiao-Dan
          Xie, Jian-Hui
          Su, Zu-Qing
          Su, Ji-Yan
          Tan, Li-Rong
          Huang, Xiao-Qi
          Chen, Jian-Nan
          Su, Zi-Ren
        affil: College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
      sug:
        subj:
          Plants, Medicinal
          Plant Extracts Pharmacodynamics
          Enzyme Inhibitors Pharmacodynamics
          Alternative Therapies
          Legumes Drug Effects
          Dose-Response Relationship, Drug
          Descriptive Statistics
          Molecular Biology
      ab: Abstract: In the present study, the inactivation effect of scutellarin (SL) on jack bean urease was investigated to elucidate the inhibitory potency, kinetics and mechanism of inhibition. It was revealed that SL acted as a concentration- and time-dependent inactivator of urease characteristic of slow-binding inhibition with an IC50 of 1.35±0.15mM. The rapid formation of the initial SL–urease complex with an inhibition constant of Ki =5.37×10−2 mM was followed by a slow isomerization into the final complex with the overall inhibition constant of Ki* =3.49×10−3 mM. High effectiveness of thiol protectors, such as L-cysteine (L-cys), 2-mercaptoethanol (2-ME) and dithiothreitol (DTT) significantly slowed down the rate of inactivation, indicating the strategic role of the active site sulfhydryl group in the blocking process. While the insignificant protection by boric acid and fluoride from the inactivation further confirmed that the active site cysteine should be obligatory for urease inhibition, which was also rationalized by the molecular docking study. The inhibition of SL on urease proved to be reversible since SL-blocked urease could be reactivated by DTT application and multidilution. The results obtained indicated that urease inactivation resulted from the reaction between SL and the sulfhydryl group.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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