Labeling the (Ca(2+)-Mg2+)-ATPase of sarcoplasmic reticulum with 4-(bromomethyl)-6,7-dimethoxycoumarin: detection of conformational changes

Biochemistry. 1992 Jul 7;31(26):6023-31. doi: 10.1021/bi00141a010.

Abstract

The (Ca(2+)-Mg2+)-ATPase of sarcoplasmic reticulum was labeled with 4-(bromomethyl)-6,7-dimethoxycoumarin. It was shown that a single cysteine residue (Cys-344) was labeled on the ATPase, with a 25% reduction in steady-state ATPase activity and no reduction in the steady-state rate of hydrolysis of p-nitrophenyl phosphate. The fluorescence intensity of the labeled ATPase was sensitive to pH, consistent with an effect of protonation of a residue of pK 6.8. Fluorescence changes were observed on binding Mg2+, consistent with binding to a single site of Kd 4 mM. Comparable changes in fluorescence intensity were observed on binding ADP in the presence of Ca2+. Binding of AMP-PCP produced larger fluorescence changes, comparable to those observed on phosphorylation with ATP or acetyl phosphate. Phosphorylation with P(i) also resulted in fluorescence changes; the effect of pH on the fluorescence changes was greater than that on the level of phosphorylation measured directly using [32P]P(i). It is suggested that different conformational states of the phosphorylated ATPase are obtained at steady state in the presence of Ca2+ and ATP and at equilibrium in the presence of P(i) and absence of Ca2+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding Sites
  • Ca(2+) Mg(2+)-ATPase / antagonists & inhibitors
  • Ca(2+) Mg(2+)-ATPase / chemistry
  • Ca(2+) Mg(2+)-ATPase / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / chemistry
  • Calcium-Transporting ATPases / metabolism*
  • Coumarins / metabolism*
  • Coumarins / pharmacology
  • Cysteine / chemistry
  • Fluorescent Dyes
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Magnesium / metabolism
  • Muscles / enzymology*
  • Phosphorylation
  • Protein Conformation
  • Rabbits
  • Sarcoplasmic Reticulum / enzymology*
  • Spectrometry, Fluorescence

Substances

  • Coumarins
  • Fluorescent Dyes
  • 4-bromomethyl-6,7-dimethoxycoumarin
  • Adenosine Triphosphate
  • Ca(2+) Mg(2+)-ATPase
  • Calcium-Transporting ATPases
  • Magnesium
  • Cysteine