Modulation of actomyosin ATPase by thiotetromycin is mediated through conformational change of actin.

ABSTRACT

Thiotetromycin isolated from the culture broth of Streptomyces sp. strain OM-674 slightly enhanced the superprecipitation and the ATPase activity of myosin B from skeletal muscle. The ATPase activity of troponin-tropomyosin-free myosin B was inhibited by thiotetromycin. The inhibitory effect of thiotetromycin was significantly attenuated by troponin-tropomyosin complex. The ATPase activity of actomyosin reconstituted from actin and myosin was inhibited by pretreatment of actin with thiotetromycin. Thiotetromycin induced a concentration-dependent decrease in the fluorescence intensity of actin and pyrenyl-F-actin. By using surface plasmon resonance (SPR), it was proved that thiotetromycin bound to actin. Thiotetromycin caused a concentration-dependent decrease in sedimentation of F-actin by hard centrifugation. This was a cross-correlation among the concentration-inhibition curves for thiotetromycin in the activity of actomyosin ATPase and the fluorescence intensity. These results suggest that thiotetromycin binds to actin to cause a conformational change, resulting in modulation of the interaction between actin and myosin, and in depolymerization of F-actin.