Allosteric modulation of cardiac myosin mechanics and kinetics by the conjugated omega‐7,9 trans‐fat rumenic acid

Key points Direct binding of rumenic acid to the cardiac myosin‐2 motor domain increases release rate for orthophosphate and Ca 2+ responsiveness muscle at low load. Physiological cellular concentrations affect ATP turnover rates super‐relaxed disordered relaxed states β‐cardiac myosin, leading a net increase in myocardial metabolic In ‐activated trabeculae, exerts direct inhibitory effect on force‐generating mechanism without affecting number motors. presence saturating actin binds with an EC 50 200 nM. Molecular docking studies provide information about site, mode binding, associated allosteric communication pathways. Free may exceed thresholds cardiomyocytes above which contractile efficiency is reduced interference small molecule therapeutics, targeting occurs. Abstract Based experiments using purified myosin domains, reconstituted actomyosin complexes rat heart ventricular we demonstrate acid, cis‐delta‐9‐trans‐delta‐11 isomer conjugated linoleic site located mammalian isoforms. case porcine varies from 10.5 μM absence nM actin. Saturating maximum basal actin‐activated ATPase activity approximately 2‐fold but decrease force output per by 23% during isometric contraction. The linked acceleration hydrolysis product orthophosphate. 5 difference 4‐fold 20‐fold. equilibrium between two functional not affected acid. Calcium increased under zero‐load conditions unchanged They show how isoform‐specific replacement residues cleft induces different non‐muscle myosin‐2C blocks skeletal smooth