title: Inhibition of Staphylococcus aureus PriA Helicase by Flavonol Kaempferol.
abstract: Staphylococcus aureus is an important etiological agent responsible for healthcare-associated infections. In this study, the effect of flavonoids on the inhibition of S. aureus PriA (SaPriA), an essential helicase for DNA replication restart, which is critical for bacterial survival, was investigated. Using vanadate-sensitive colorimetric assay, the concentration of phosphate, from ATP hydrolysis by SaPriA, was decreased to 37 and 69%, respectively, in the presence of 35 μM kaempferol and myricetin. The effect of quercetin, galangin, dihydromyricetin, and myricitrin was insignificant. From titration curve, IC50 of kaempferol for SaPriA was determined to be 22 ± 2 μM. Using fluorescence quenching, we identified that kaempferol can bind to SaPriA with K(d) of 9.1 ± 3.2 μM. To our knowledge, these preliminary results constituted the first study regarding that naturally occurring product such as flavonols kaempferol and myricetin can be potent inhibitors targeting PriA.
authors.affiliation: School of Biomedical Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung City, Taiwan.
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Huang
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Huang
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Kai-Jr
authors.initials: KJ
authors.lastname: Yang
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D044949:Kaempferols / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D005419:Flavonoids; D044949:Kaempferols; C006552:kaempferol; D004265:DNA Helicases