Characterisation of ATP binding inhibition to the sarcoplasmic reticulum Ca(2+)-ATPase by thapsigargin.
The inhibition of Ca(2+)-ATPase of sarcoplasmic reticulum by thapsigargin has been reported to be associated with a suppression of calcium binding to the high affinity transport sites. We report here that thapsigargin also acts as an inhibitor of ATP binding by reducing its apparent affinity by about two orders of magnitude. This inhibition is non-competitive indicating that thapsigargin does not bind to the ATP binding site. This is confirmed by the fact that thapsigargin binding to the Ca(2+)-ATPase does not affect the binding of 2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-ATP (TNP-ATP).
DeJesus
F
F
Département de Biologie Moléculaire et Structurale, Centre d'Etudes Nucléaires de Grenoble, France.
Girardet
J L
JL
Dupont
Y
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D011485:Protein Binding; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D013050:Spectrometry, Fluorescence; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D013729:Terpenes; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases