Omecamtiv mecarbil enhances the duty ratio of human β-cardiac myosin resulting in increased calcium sensitivity and slowed force development in cardiac muscle

AM Swenson, W Tang, CA Blair, CM Fetrow… - Journal of Biological …, 2017 - ASBMB
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 …