Demethoxycurcumin is a potent inhibitor of P-type ATPases from diverse kingdoms of life

TY - JOUR

T1 - Demethoxycurcumin is a potent inhibitor of P-type ATPases from diverse kingdoms of life

AU - Dao, Trong Tuan

AU - Sehgal, Pankaj

AU - Thanh Tung, Truong

AU - Møller, Jesper Vuust

AU - Nielsen, John

AU - Palmgren, Michael Broberg

AU - Christensen, Søren Brøgger

AU - Fuglsang, Anja Thoe

PY - 2016/9

Y1 - 2016/9

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1371/journal.pone.0163260

DO - 10.1371/journal.pone.0163260

M3 - Journal article

C2 - 27644036

SN - 1932-6203

VL - 11

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 9

M1 - e0163260

ER -