Kinetic mechanism of 1-N6-etheno-2-aza-ATP and 1-N6-etheno-2-aza-ADP binding to bovine ventricular actomyosin-S1 and myofibrils

J Biol Chem. 1985 Dec 5;260(28):15156-62.

Abstract

The fluorescence emission of 1-N6-etheno-2-aza-ATP (epsilon-aza-ATP) at 410-460 nm is enhanced approximately 8-fold upon mixing substoichiometric concentrations of epsilon-aza-ATP with bovine cardiac actomyosin-S1 or myofibrils. The time course of nucleotide fluorescence measured in a front face stopped flow cell upon mixing epsilon-aza-ATP with bovine cardiac myofibrils ([Ca2+] less than 10(-7) M) is essentially the same as that with bovine cardiac actomyosin subfragment-1. In single turnover experiments, the fluorescence rapidly rises to a maximum value, then decreases with a rate constant of 0.04 s-1 at 0 degree C to a final value that is approximately twice the level of the unbound nucleotide. At concentrations of epsilon-aza-ATP greater than 40 microM the kinetics of epsilon-aza-ATP binding is clearly biphasic for both actomyosin-S1 and myofibrils. At 0 degree C, the rate of the more rapid phase is proportional to nucleotide concentration and has a second order rate constant of 1.7 X 10(5) M-1 s-1; the rate of the slower phase extrapolates to a maximum of 4-5 s-1 at high nucleotide concentration. The rate constants for dissociation of epsilon-aza-ADP from bovine cardiac actomyosin-S1 and myofibrils were measured from the decrease in epsilon-aza-ADP fluorescence enhancement observed upon displacement by ATP to be 20 and 18 s-1, respectively, at 0 degree C. These results indicate that most of the cross-bridges in cardiac myofibrils are bound to actin and that the geometric constraints imposed upon the interaction of actin and myosin by the three-dimensional structure of the myofibril do not modify the kinetics of epsilon-aza-ATP binding or epsilon-aza-ADP dissociation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives*
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / analogs & derivatives*
  • Animals
  • Cattle
  • Ethenoadenosine Triphosphate / analogs & derivatives*
  • Ethenoadenosine Triphosphate / metabolism
  • Flow Cytometry
  • Kinetics
  • Mathematics
  • Myocardium / enzymology*
  • Myofibrils / metabolism*
  • Myosin Subfragments
  • Myosins / metabolism*
  • Peptide Fragments / metabolism*
  • Spectrometry, Fluorescence

Substances

  • Ethenoadenosine Triphosphate
  • Myosin Subfragments
  • Peptide Fragments
  • aza-epsilon-ADP
  • aza-epsilon-ATP
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Myosins