Screening and Evaluation of Ruminal Bacterial Urease Inhibitors

  • ZHANG Zhenyu ,
  • ZHAO Shengguo ,
  • ZHENG Nan ,
  • WANG Jiaqi
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  • 1. State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
    2. Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Received date: 2020-01-09

  Online published: 2020-06-16

Abstract

In this study, a novel ruminal bacterial urease inhibitor was obtained by targeting bacterial urease structure (PDB_ID 4EP8) with molecular docking based virtual screening to filter through ChemDiv compound database followed by ruminal urease activity test. This compound was N-(3,4-dimethoxybenzyl)-2-{(4S)-1-[2-(1H-indol-3-yl) ethyl]-2,5-dioxoimidazolidin-4-yl} acetamide, and it’s IC50 value was 101.4 μmol/L. Ruminal urease kinetics experiments showed that the compound was a mix-type urease inhibitor. In vitro anaerobic culture experiments demonstrated that the compound could inhibit ruminal bacteria ammonia nitrogen production. Molecular docking illustrated that the compound could combine with some key amino acid residues in the urease active site and the flexible loop region outside the urease active site. This compound has a fair urease inhibition capacity, and it can be used for lead optimization, which laid a groundwork for further development of novel urease inhibitors.

Cite this article

ZHANG Zhenyu , ZHAO Shengguo , ZHENG Nan , WANG Jiaqi . Screening and Evaluation of Ruminal Bacterial Urease Inhibitors[J]. Chinese Journal of Animal Nutrition, 2020 , 32(6) : 2850 -2860 . DOI: 10.3969/j.issn.1006-267x.2020.06.045

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