Emodin targets the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: enzymatic inhibition assay with crystal structural and thermodynamic characterization.

Full Abstract

BACKGROUND: The natural product Emodin demonstrates a wide range of pharmacological properties including anticancer, anti-inflammatory, antiproliferation, vasorelaxant and anti-H. pylori activities. Although its H. pylori inhibition was discovered, no acting target information against Emodin has been revealed to date. RESULTS: Here we reported that Emodin functioned as a competitive inhibitor against the recombinant beta-hydroxyacyl-ACP dehydratase from Helicobacter pylori (HpFabZ), and strongly inhibited the growth of H. pylori strains SS1 and ATCC 43504. Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) based assays have suggested the kinetic and thermodynamic features of Emodin/HpFabZ interaction. Additionally, to inspect the binding characters of Emodin against HpFabZ at atomic level, the crystal structure of HpFabZ-Emodin complex was also examined. The results showed that Emodin inhibition against HpFabZ could be implemented either through its occupying the entrance of the tunnel or embedding into the tunnel to prevent the substrate from accessing the active site. CONCLUSION: Our work is expected to provide useful information for illumination of Emodin inhibition mechanism against HpFabZ, while Emodin itself could be used as a potential lead compound for further anti-bacterial drug discovery.

Author information

Author/s: Chen, Jing (J); Zhang, Liang (L); Zhang, Yu (Y); Zhang, Haitao (H); Du, Jiamu (J); Ding, Jianping (J); Guo, Yuewei (Y); Jiang, Hualiang (H); Shen, Xu (X);

Affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. jingchen(-atsign-)mail.shcnc.ac.cn

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: BMC microbiology (BMC Microbiol), published in England. (Language: eng)

Reference: 2009-; vol 9 (issue ) : pp 91

Dates: Created 2009/06/09; Completed 2009/06/29;

PMID: 19433000, status: MEDLINE (last retrieval date: 6/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Bacterial Proteins - antagonists & inhibitors
Calorimetry
Catalytic Domain
Emodin - pharmacokinetics
Enzyme Inhibitors - pharmacokinetics

Associated Chemicals: Bacterial Proteins (0) ; Enzyme Inhibitors (0) ; Emodin (518-82-1) ; Hydro-Lyases (EC 4.2.1.-) ; beta-hydroxyacyl-(acyl-carrier-protein)dehydrase (EC 4.2.1.-)

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