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Myofibrillar creatine kinase activity inferred from a 3D model
J A Mejsnar1, B Sopko, M Gregor
1Faculty of Science, Charles University, Prague, Czech Republic. mejsnar@natur.cuni.cz
Physiological Research
|June 20, 2002
Summary
Myofibrillar creatine kinase (CK) undergoes conformational changes upon substrate binding, transitioning between open, closed, and intermediary states. These changes are crucial but not sufficient for enzyme activity, indicating other cellular controls are involved.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- Myofibrillar creatine kinase (CK) plays a vital role in buffering ATP during muscle energy metabolism.
- Understanding the enzyme's conformational changes is key to elucidating cellular control of enzyme activity.
Purpose of the Study:
- To compute the force field for three energetic states of myofibrillar creatine kinase (CK).
- To investigate substrate-induced conformational changes and their relation to enzyme activity.
Main Methods:
- Computational analysis of the force field for substrate-free CK, MgATP-bound CK, and MgATP-creatine-bound CK.
- Examination of enzyme conformations: inactive "open", reactive "closed", and nonreactive "intermediary" states.
Main Results:
- The substrate-free CK molecule adopts an inactive "open" conformation.
- Binding of MgATP induces a reactive "closed" conformation.
- Subsequent binding of creatine leads to a nonreactive "intermediary" conformation.
- Substrate-induced conformational changes alone are insufficient to guarantee CK activity.
Conclusions:
- Cellular control mechanisms beyond substrate binding are essential for the transition from the intermediary to the active closed conformation of CK.
- Acid-base catalysis is the fundamental principle for phosphoryl group transfer in CK reactions.