Metal cation controls phosphate release in the myosin ATPase

Area of Science:

• Biochemistry
• Enzymology
• Muscle Contraction

Background:

• Myosin is an enzyme that uses ATP to generate force.
• The rate of myosin's reverse recovery stroke is influenced by the metal cation complexed with ATP.
• This stroke is slow with MgATP and fast with MnATP, suggesting differences in phosphate binding and release.

Purpose of the Study:

• To investigate the role of metal cations, specifically magnesium (Mg) and manganese (Mn), in the mechanism of phosphate release from myosin.
• To understand how electrostatic interactions and ionic potential influence phosphate retention in the myosin active site.

Main Methods:

• Analysis of octahedral complexes of magnesium and manganese.
• Utilizing stable myosin-nucleotide analog complexes.
• Employing Raman spectroscopy to probe the γ-phosphate analog's position relative to ADP.

Main Results:

• Magnesium ions have a higher partial charge than manganese ions.
• Manganese ions have a smaller ionic potential due to their larger size.
• Raman spectroscopy revealed the γ-phosphate analog is 0.01 nm further from ADP in the manganese complex compared to the magnesium complex.

Conclusions:

• The ionic potential of the metal cation significantly influences the retention of abstracted phosphate in the myosin active site.
• Electrostatic forces, dictated by the metal cation's charge and ionic potential, play a crucial role in regulating phosphate release kinetics during the myosin power cycle.