title: Demethoxycurcumin Is A Potent Inhibitor of P-Type ATPases from Diverse Kingdoms of Life.
abstract: P-type ATPases catalyze the active transport of cations and phospholipids across biological membranes. Members of this large family are involved in a range of fundamental cellular processes. To date, a substantial number of P-type ATPase inhibitors have been characterized, some of which are used as drugs. In this work a library of natural compounds was screened and we first identified curcuminoids as plasma membrane H+-ATPases inhibitors in plant and fungal cells. We also found that some of the commercial curcumins contain several curcuminoids. Three of these were purified and, among the curcuminoids, demethoxycurcumin was the most potent inhibitor of all tested P-type ATPases from fungal (Pma1p; H+-ATPase), plant (AHA2; H+-ATPase) and animal (SERCA; Ca2+-ATPase) cells. All three curcuminoids acted as non-competitive antagonist to ATP and hence may bind to a highly conserved allosteric site of these pumps. Future research on biological effects of commercial preparations of curcumin should consider the heterogeneity of the material.
authors.affiliation: Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Trong Tuan
authors.initials: TT
authors.lastname: Dao
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sehgal
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Truong Thanh
authors.initials: TT
authors.lastname: Tung
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Jesper Vuust
authors.initials: JV
authors.lastname: Møller
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Palmgren
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Søren Brøgger
authors.initials: SB
authors.lastname: Christensen
authors.affiliation: Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anja Thoe
authors.identifier: http://orcid.org/0000-0003-1153-8394
authors.initials: AT
authors.lastname: Fuglsang
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D036381:Diarylheptanoids; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D018724:Spinacia oleracea / Q000201:enzymology*
chemical_list: D036381:Diarylheptanoids; D004791:Enzyme Inhibitors; D000251:Adenosine Triphosphatases; D003474:Curcumin; C050229:demethoxycurcumin