Modulation of actomyosin ATPase by thiotetromycin is mediated through conformational change of actin.
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.
Nakatani
K
K
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan.
Murayama
T
T
Satoh
Y
Y
Furukawa
K I
KI
Omura
S
S
Ohizumi
Y
Y
D000199:Actins / Q000737:chemistry / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D009218:Myosins / Q000187:drug effects* / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D011817:Rabbits; D013302:Streptomyces; D013876:Thiophenes / Q000494:pharmacology
D000199:Actins; D000900:Anti-Bacterial Agents; D013876:Thiophenes; C037482:thiotetromycin; D009218:Myosins