Effects of divalent cations bound to the catalytic site on ATP-induced conformational changes in the sarcoplasmic reticulum Ca(2+)-ATPase: stopped-flow analysis of the fluorescence of N-acetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine attached to cysteine-674

Biochemistry. 1994 Jul 12;33(27):8240-6. doi: 10.1021/bi00193a010.

Abstract

Cys-674 of the sarcoplasmic reticulum Ca(2+)-ATPase was labeled with N-acetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine without a loss of the catalytic activity. The steady-state fluorescence of the label decreased with increasing concentration of Mg.ATP, Mn.ATP, or Ca.ATP in the presence of Ca2+ and 0.1 M KCl at 0 degree C, pH 7.0. The maximum extent of the decrease was 23%. The Mg.ATP-, Mn.ATP-, or Ca.ATP-induced fluorescence drop was also determined by the stopped-flow spectrofluorometry. The Ca.ATP-induced fluorescence drop manifested a biphasic time course. The first phase reflects the conformational change which was previously shown [Suzuki, H., Obara, M., Kuwayama, H., & Kanazawa, T. (1987) J. Biol. Chem. 262, 15448-15456] to occur upon formation of the calcium-enzyme-substrate complex. The amplitude of the second phase was 2.5% of the fluorescence before addition of Ca.ATP. This phase of the fluorescence drop coincided with the phosphoenzyme formation, which was determined by the continuous flow-rapid quenching method. The phosphoenzyme formed was largely sensitive to ADP. When adenosine 5'-(beta,gamma-methylenetriphosphate) (a nonhydrolyzable ATP analog incapable of phosphorylating the enzyme) was added in the presence of 5 mM CaCl2 without added MgCl2 the steady-state fluorescence decreased rapidly by 20%. However, this drop lacked the second phase. When phosphoenzyme isomerization from the ADP-sensitive form to the ADP-insensitive form was prevented by the N-ethylmaleimide treatment, the second phase of the Ca.ATP-induced fluorescence drop again coincided with the phosphoenzyme formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Binding Sites
  • Calcium-Transporting ATPases / chemistry*
  • Calcium-Transporting ATPases / metabolism
  • Catalysis
  • Cations, Divalent
  • Cysteine / metabolism*
  • Ethylmaleimide / pharmacology
  • Fluorescent Dyes*
  • Kinetics
  • Muscles / enzymology
  • Naphthalenesulfonates*
  • Protein Conformation / drug effects
  • Rabbits
  • Sarcoplasmic Reticulum / enzymology*
  • Spectrometry, Fluorescence

Substances

  • Cations, Divalent
  • Fluorescent Dyes
  • Naphthalenesulfonates
  • 5-((2-aminoethyl)amino)naphthalene-1-sulfonic acid
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Calcium-Transporting ATPases
  • Cysteine
  • Ethylmaleimide