Emodin targets the β-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: enzymatic inhibition assay with crystal structural and thermodynamic characterizationReportar como inadecuado




Emodin targets the β-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: enzymatic inhibition assay with crystal structural and thermodynamic characterization - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Microbiology

, 9:91

First Online: 12 May 2009Received: 25 November 2008Accepted: 12 May 2009

Abstract

BackgroundThe 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.

ResultsHere we reported that Emodin functioned as a competitive inhibitor against the recombinant β-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.

ConclusionOur 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.

AbbreviationsEmodin3-methyl-1, 6, 8-trihydroxyanthraquinone

anti-H. pylorianti-Helicobacter pylori

HpFabZβ-hydroxyacyl-ACP dehydratase from Helicobacter pylori

SPRsurface plasmon resonance

ITCisothermal titration calorimetry

HpHelicobacter pylori

FAS IIthe type II fatty acid synthetic pathway

FabZβ-hydroxyacyl-ACP

TCMtraditional Chinese medicine

VEGFvascular endothelial growth factor

DMSODimethyl sulfoxide

MRmolecular replacement

MICminimum inhibitory concentration

RUsresonance units

kaassociation rate constant

kddissociation rate constant

KDequilibrium dissociation constant.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2180-9-91 contains supplementary material, which is available to authorized users.

Jing Chen, Liang Zhang contributed equally to this work.

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Autor: Jing Chen - Liang Zhang - Yu Zhang - Haitao Zhang - Jiamu Du - Jianping Ding - Yuewei Guo - Hualiang Jiang - Xu Shen

Fuente: https://link.springer.com/article/10.1186/1471-2180-9-91







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