title: A unique mechanism of curcumin inhibition on F1 ATPase.
abstract: ATP synthase (F-ATPase) function depends upon catalytic and rotation cycles of the F1 sector. Previously, we found that F1 ATPase activity is inhibited by the dietary polyphenols, curcumin, quercetin, and piceatannol, but that the inhibitory kinetics of curcumin differs from that of the other two polyphenols (Sekiya et al., 2012, 2014). In the present study, we analyzed Escherichia coli F1 ATPase rotational catalysis to identify differences in the inhibitory mechanism of curcumin versus quercetin and piceatannol. These compounds did not affect the 120° rotation step for ATP binding and ADP release, though they significantly increased the catalytic dwell duration for ATP hydrolysis. Analysis of wild-type F1 and a mutant lacking part of the piceatannol binding site (γΔ277-286) indicates that curcumin binds to F1 differently from piceatannol and quercetin. The unique inhibitory mechanism of curcumin is also suggested from its effect on F1 mutants with defective β-γ subunit interactions (γMet23 to Lys) or β conformational changes (βSer174 to Phe). These results confirm that smooth interaction between each β subunit and entire γ subunit in F1 is pertinent for rotational catalysis.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, and Futai Special Laboratory, Yahaba, Iwate 028-3694, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Sekiya
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, and Futai Special Laboratory, Yahaba, Iwate 028-3694, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hisasaka
authors.affiliation: Department of Bioscience, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga 526-0829, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Iwamoto-Kihara
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, and Futai Special Laboratory, Yahaba, Iwate 028-3694, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Futai
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, and Futai Special Laboratory, Yahaba, Iwate 028-3694, Japan. Electronic address: nakanim@iwate-med.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakanishi-Matsui
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003474:Curcumin / Q000737:chemistry*; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000648:ultrastructure*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D006180:Proton-Translocating ATPases; D003474:Curcumin
keywords: ATP synthase; ATPase rotational catalysis; Curcumin; F(1) ATPase; Piceatannol; Quercetin