Structural Dynamics of Myosin's Force-Generating Domain with Drug Inhibitor Blebbistatin

Presenter Information

Amanda Bernarde, Minnesota State University Mankato

Location

CSU Ballroom

Start Date

18-4-2016 10:00 AM

End Date

18-4-2016 11:30 AM

Student's Major

Chemistry and Geology

Student's College

Science, Engineering and Technology

Mentor's Name

Rebecca Moen

Mentor's Department

Chemistry and Geology

Mentor's College

Science, Engineering and Technology

Description

Myosin and actin are the two vital components of every muscle contained within the body. The cross-bridging that occurs between these two components, in combination with harvested energy from breaking a bond of adenosine triphosphate (ATP), will cause muscle contractions. When energy is scarce or an inhibitor is present, the myosin-actin complex is unable to generate normal muscle contraction. Blebbistatin, a potent myosin II drug inhibitor, stops myosin from breaking down subsequent ATP molecules by impeding the component’s ability to release the ATP hydrolysis products, thus halting the cross-bridging cycle before a contraction can occur. Myosin is spin-labeled at a cysteine amino acid residue located in the SH1 helix, a crucial alpha-helix in the force-generating domain of myosin. Myosin’s function, the ability to bind and hydrolyze ATP, was tested with blebbistatin-induced inhibition of ~80% of wildtype myosin activity. By combining spin-labeled myosin and actin, electron paramagnetic resonance (EPR) was used to compare the structural dynamics when the system is in the presence and absence of blebbistatin. Indication of structural changes can supplement research information pertaining to the drug and can also help further understand the mechanism of blebbistatin inhibition in future studies.