title: Caffeic acid phenethyl ester (CAPE), an active component of propolis, inhibits Helicobacter pylori peptide deformylase activity.
abstract: Helicobacter pylori (H. pylori) is a major causative factor for gastrointestinal illnesses, H. pylori peptide deformylase (HpPDF) catalyzes the removal of formyl group from the N-terminus of nascent polypeptide chains, which is essential for H. pylori survival and is considered as a promising drug target for anti-H. pylori therapy. Propolis, a natural antibiotic from honeybees, is reported to have an inhibitory effect on the growth of H. pylori in vitro. In addition, previous studies suggest that the main active constituents in the propolis are phenolic compounds. Therefore, we evaluated a collection of phenolic compounds derived from propolis for enzyme inhibition against HpPDF. Our study results show that Caffeic acid phenethyl ester (CAPE), one of the main medicinal components of propolis, is a competitive inhibitor against HpPDF, with an IC50 value of 4.02 μM. Furthermore, absorption spectra and crystal structural characterization revealed that different from most well known PDF inhibitors, CAPE block the substrate entrance, preventing substrate from approaching the active site, but CAPE does not have chelate interaction with HpPDF and does not disrupt the metal-dependent catalysis. Our study provides valuable information for understanding the potential anti-H. pylori mechanism of propolis, and CAPE could be served as a lead compound for further anti-H. pylori drug discovery.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Kunqiang
authors.initials: K
authors.lastname: Cui
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Lu
authors.forename: Lili
authors.initials: L
authors.lastname: Zhu
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D002109:Caffeic Acids / Q000737:chemistry*; D016480:Helicobacter pylori / Q000201:enzymology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry; D011429:Propolis / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D002109:Caffeic Acids; D011429:Propolis; D000581:Amidohydrolases; C084507:peptide deformylase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol