1-O-Sulfatobastadins-1 and -2 from Ianthella basta (Pallas). Antagonists of the RyR1-FKBP12 Ca2+ Channel
نویسندگان
چکیده
Two new sulfate monoesters of hemibastadins-1 and -2 were isolated from the marine sponge Ianthella basta (Pallas) from Guam. A third new compound was tentatively assigned the structure 34-O-sulfatobastadin-9. The 1-O-sulfatohemibastadins-1 and –2 were antagonists of the RyR1-FKBP12 Ca channel under conditions where the known compound bastadin-5 exhibits potent agonism (EC50 2 μM).
منابع مشابه
FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes.
The skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel or ryanodine receptor (RyR1) binds four molecules of FKBP12, and the interaction of FKBP12 with RyR1 regulates both unitary and coupled gating of the channel. We have characterized the physiologic effects of previously identified mutations in RyR1 that disrupt FKBP12 binding (V2461G and V2461I) on excitation-contraction (EC) c...
متن کاملCoupled gating between individual skeletal muscle Ca2+ release channels (ryanodine receptors)
Excitation-contraction coupling in skeletal muscle requires the release of intracellular calcium ions (Ca2+) through ryanodine receptor (RyR1) channels in the sarcoplasmic reticulum. Half of the RyR1 channels are activated by voltage-dependent Ca2+ channels in the plasma membrane. In planar lipid bilayers, RyR1 channels exhibited simultaneous openings and closings, termed "coupled gating." Addi...
متن کاملPKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle
The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation....
متن کاملRyanodine receptor binding to FKBP12 is modulated by channel activation state.
Ryanodine receptor (RyR) Ca2+ release channels undergo a conformational change between the open and closed states. Its protein modulator, FK506 binding protein 12 (FKBP12), stabilises the channel gating between the four subunits that surround a central Ca2+-conducting pore. To understand the interdependence of RyR and FKBP12 binding, physiological and pharmacological agents were used to modulat...
متن کاملCharacterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor.
We investigated the interaction of the 12 kDa FK506-binding protein (FKBP12) with two ryanodine-receptor isoforms (RyR1 and RyR3) and with two myo-inositol 1,4,5-trisphosphate (IP3) receptor isoforms (IP3R1 and IP3R3). Using glutathione S-transferase (GST)-FKBP12 affinity chromatography, we could efficiently extract RyR1 (42+/-7% of the solubilized RyR1) from terminal cisternae of skeletal musc...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 2 شماره
صفحات -
تاریخ انتشار 2004