Evaluation of the inhibition of chlorophenols towards human cytochrome P450 3A4 and differences among various species

Liu, Nai-Rong; Yang, Kai Chiang; Li, Wenting; Pang, Zhihua; Zhang, Qing; Wang, Jiajia; Dang, Wenxi; Jia, Ruo-Yong; Fu, Zhiwei; Li, Yixuan; Yao, Zhuhua; Fang, Zhong‐Ze

doi:10.1016/j.scitotenv.2020.138187

Cited by 11 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After that, the molecular docking was calculated by the genetic algorithm (GA) method, in which the number of GA runs was 10, the GA population size was 150, and maximum number of energy evolutions was set to 25,000,000. Ten poses were generated for each compound with different binding energy, and the lowest energy structure was considered as the best docking pose [ 55 ]. The software AutoDockTools was used to predict the inhibition constant (K i ) of small compounds and proteins.…”

Section: Methodsmentioning

confidence: 99%

Chelerythrine Chloride: A Potential Rumen Microbial Urease Inhibitor Screened by Targeting UreG

Zhang

Xiong

et al. 2021

IJMS

View full text Add to dashboard Cite

Inhibition of ruminal microbial urease is of particular interest due to its crucial role in regulating urea-N utilization efficiency and nitrogen pollution in the livestock industry. Acetohydroxamic acid (AHA) is currently the only commercially available urease inhibitor, but it has adverse side effects. The urease accessory protein UreG, which facilitates the functional incorporation of the urease nickel metallocentre, has been proposed in developing urease inhibitor through disrupting urease maturation. The objective of this study was to screen natural compounds as potential urease inhibitors by targeting UreG in a predominant ruminal microbial urease. In silico screening and in vitro tests for potential inhibitors were performed using molecular docking and an assay for the GTPase activity of UreG. Chelerythrine chloride was selected as a potential urease inhibitor of UreG with an inhibition concentration IC50 value of 18.13 μM. It exhibited mixed inhibition, with the Ki value being 26.28 μM. We further explored its inhibition mechanism using isothermal titration calorimetry (ITC) and circular dichroism (CD) spectroscopy, and we found that chelerythrine chloride inhibited the binding of nickel to UreG and induced changes in the secondary structure, especially the α-helix and β-sheet of UreG. Chelerythrine chloride formed a pi-anion interaction with the Asp41 residue of UreG, which is an important residue in initiating the conformational changes of UreG. In conclusion, chelerythrine chloride exhibited a potential inhibitory effect on urease, which provided new evidence for strategies to develop novel urease inhibitors targeting UreG to reduce nitrogen excretion from ruminants.

show abstract

Section: Methodsmentioning

confidence: 99%