Myofibrillar Creatine Kinase Activity Inferred from a 3D Model

J. A. MEJSNAR, B. SOPKO, M. GREGOR

Faculty of Science, Charles University, Prague, Czech Republic

Received January 16, 2001
Accepted June 6, 2001

Summary
Myofibrillar creatine kinase (CK) that buffers ATP during fluctuating muscle energy metabolism has been selected for studies of conformational changes underlying the cellular control of enzyme activity. The force field was computed for three energetic states, namely for the substrate-free CK molecule, for the molecule conjugated with the MgATP complex, and for the molecule conjugated with the pair of reactants MgATP-creatine. Without its substrates, the enzyme molecule assumes an inactive "open" form. Upon binding of the MgATP complex, the CK molecule takes up a reactive "closed" conformation. Subsequent binding of creatine yields a nonreactive "intermediary" conformation. Acid-base catalysis is considered to be the basic principle for the reversible transfer of the phosphoryl group between the substrates. The results indicate that the substrate-induced energy minimizing conformational changes do not represent a sufficient condition for CK activity and that some other essential component of physiological control at the cellular level is involved in the transition from the intermediary to the closed structure of the molecule.

Key words
Muscle · Energetics · Myofibrillar creatine kinase

Reprint requests
Jiří Mejsnar, Charles University, Faculty of Science, Department of Physiology and Developmental Biology,Viničná 7, Praha 2, CZ-128 44, Czech Republic, e-mail: mejsnar@natur.cuni.cz