A unique mechanism of curcumin inhibition on F1 ATPase

Mizuki Sekiya; Ryosuke Hisasaka; Atsuko Iwamoto-Kihara; Masamitsu Futai; Mayumi Nakanishi-Matsui

doi:10.1016/j.bbrc.2014.09.027

A unique mechanism of curcumin inhibition on F1 ATPase

Biochem Biophys Res Commun. 2014 Oct 3;452(4):940-4. doi: 10.1016/j.bbrc.2014.09.027. Epub 2014 Sep 16.

Authors

Mizuki Sekiya¹, Ryosuke Hisasaka¹, Atsuko Iwamoto-Kihara², Masamitsu Futai¹, Mayumi Nakanishi-Matsui³

Affiliations

¹ Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, and Futai Special Laboratory, Yahaba, Iwate 028-3694, Japan.
² Department of Bioscience, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga 526-0829, Japan.
³ 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.

PMID: 25230139
DOI: 10.1016/j.bbrc.2014.09.027

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.

Keywords: ATP synthase; ATPase rotational catalysis; Curcumin; F(1) ATPase; Piceatannol; Quercetin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
Curcumin / chemistry*
Enzyme Activation
Models, Chemical
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Conformation
Proton-Translocating ATPases / antagonists & inhibitors*
Proton-Translocating ATPases / ultrastructure*
Structure-Activity Relationship
Substrate Specificity

Substances

Proton-Translocating ATPases
Curcumin