But in solution, six monomers were highly symmetric and the β3 strands might exhibit much more flexible conformation to allow Emodin to enter into the active tunnels of all the six monomers, resulting in a
1:1 stoichiometry for HpFabZ/Emodin complex formation. In addition, we also confirmed that Emodin could inhibit the growth of H. pylori strains SS1 (MIC: 5 μg/ml) and ATCC 43504 (MIC: 10 μg/ml). We could thereby suppose that the inhibition against HpFabZ might be one of the key factors for its H. plori strain inhibition, although there are maybe other undiscovered acting targets for Emodin. Recently, apart from Emodin, some other HpFabZ inhibitors have been discovered to inhibit the growth of H. pylori. For example, Juglone, a natural product, was reported to selleck chemical inhibit the growth of H. pylori strains SS1 with find more MIC value of 5 μg/ml . Three flavonoids (Quercetin, Apigenin and (S)-Sakuranetin) inhibited H. pylori strains ATCC 43504 at MIC values of 100, 25, 25 μg/ml, respectively . All these inhibitors shared the same competitive inhibition mechanism against HpFabZ and bound to the same residues of the binding site from HpFabZ. Conclusion Summarily, Emodin was firstly discovered as a competitive inhibitor against HpFabZ. The kinetic and thermodynamic characterization of Emodin/HpFabZ
interaction has been completely performed by SPR and ITC based assays. The analyzed HpFabZ/Emodin complex crystal structure has clearly suggested that the inhibition
of Emodin against HpFabZ could be carried out either by its occupying the entrance of the tunnel or plugging the tunnel to prevent the substrate from accessing the active site. Our work is expected to shed light on the potential inhibitory mechanism of Emodin against HpFabZ, while Emodin has been suggested to be a potential lead compound for further anti-bacterial drug discovery. Selleck Talazoparib Acknowledgements This work was supported by the National Natural Science Foundation of China (grants 30525024, 90713046, 20721003) and CAS Foundation (grant KSCX2-YW-R-18). Electronic supplementary material Additional file 1: Supplemental Materials. Supplemental Figure Legends. (DOC 28 KB) Additional file 2: Supplemental many Figure S1. pH profile of HpFabZ enzyme activity. (PDF 224 KB) Additional file 3: Supplemental Figure S2. The effect of DMSO on HpFabZ enzyme activity. (PDF 562 KB) References 1. Marshall BJ, Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984, 1:1311–1315.CrossRefPubMed 2. Cover TL, Blaser MJ:Helicobacter pylori infection, a paradigm for chronic mucosal inflammation: pathogenesis and implications for eradication and prevention. Adv Intern Med 1996, 41:85–117.PubMed 3. Brown LM:Helicobacter pylori : epidemiology and routes of transmission. Epidemiol Rev 2000, 22:283–297.PubMed 4.