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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward
Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward
Doctoral Dissertations
Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …
Investigatin Actin-Myosin Mechanics To Model Heart Disease Using Fluorescence Microscopy And Optical Trapping, Justin Edward Reynolds
Investigatin Actin-Myosin Mechanics To Model Heart Disease Using Fluorescence Microscopy And Optical Trapping, Justin Edward Reynolds
Honors Theses
Hypertrophic cardiomyopathy (HCM) is a hereditary disease in which the myocardium becomes hypertrophied, making it more difficult for the heart to pump blood. HCM is commonly caused by a mutation in the β-cardiac myosin II heavy chain. Myosin is a motor protein that facilitates muscle contraction by converting chemical energy from ATP hydrolysis into mechanical work and concomitantly moving along actin filaments. Optical tweezers have been used previously to analyze single myosin biophysical properties; however, myosin does not work as a single unit within the heart. Multiple myosin interacts to displace actin filaments and do not have the same properties …
Omecamtiv Mecarbil Enhances The Duty Ratio Of Human Β-Cardiac Myosin Resulting In Increased Calcium Sensitivity And Slowed Force Development In Cardiac Muscle, Anja M. Swenson, Wanjian Tang, Cheavar A. Blair, Christopher M. Fetrow, William C. Unrath, Michael J. Previs, Kenneth S. Campbell, Christopher M. Yengo
Omecamtiv Mecarbil Enhances The Duty Ratio Of Human Β-Cardiac Myosin Resulting In Increased Calcium Sensitivity And Slowed Force Development In Cardiac Muscle, Anja M. Swenson, Wanjian Tang, Cheavar A. Blair, Christopher M. Fetrow, William C. Unrath, Michael J. Previs, Kenneth S. Campbell, Christopher M. Yengo
Physiology Faculty Publications
The small molecule drug omecamtiv mecarbil (OM) specifically targets cardiac muscle myosin and is known to enhance cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear. We expressed and purified human β-cardiac myosin subfragment 1 (M2β-S1) containing a C-terminal Avi tag. We demonstrate that the maximum actin-activated ATPase activity of M2β-S1 is slowed more than 4-fold in the presence of OM, whereas the actin concentration required for half-maximal ATPase was reduced dramatically (30-fold). We find OM does not change the overall actin affinity. Transient kinetic experiments suggest that there are …
Mechanism Of Catch Force: Tethering Of Thick And Thin Filaments By Twitchin., Thomas M Butler, Marion J Siegman
Mechanism Of Catch Force: Tethering Of Thick And Thin Filaments By Twitchin., Thomas M Butler, Marion J Siegman
Department of Molecular Physiology and Biophysics Faculty Papers
Catch is a mechanical state occurring in some invertebrate smooth muscles characterized by high force maintenance and resistance to stretch during extremely slow relaxation. During catch, intracellular calcium is near basal concentration and myosin crossbridge cyctng rate is extremely slow. Catch force is relaxed by a protein kinase A-mediated phosphorylation of sites near the N- and C- temini of the minititin twitchin (approximately 526 kDa). Some catch force maintenance car also occur together with cycling myosin crossbridges at submaximal calcium concentrations, but not when the muscle is maximally activated. Additionally, the link responsible for catch can adjust during shortening of …