A novel type of phospholipase A2 inhibitor, thielocin A1 beta, and mechanism of action.
Thielocin A1 beta, a novel phospholipase A2 inhibitor, was isolated from Thielavia terricola RF-143. It inhibited various phospholipase A2s in a dose-dependent manner. Among these, group II phospholipase A2 from rat was most sensitive to thielocin A1 beta (IC50 = 0.0033 microM). The inhibition of phospholipase A2 by thielocin A1 beta was independent of Ca2+ and substrate concentration. In addition, the inhibition of rat group II phospholipase A2 was noncompetitive (Ki = 0.0068 microM) and reversible. Furthermore, thielocin A1 beta quenched the relative fluorescent intensity of Naja naja venom phospholipase A2 and in a dose-dependent manner; 50% quench was noted with a molar ratio of thielocin A1 beta/enzyme of 2.2. These observations indicated that inhibition of phospholipase A2 by thielocin A1 beta may result from direct interaction with the enzyme.
Tanaka
K
K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Matsutani
S
S
Matsumoto
K
K
Yoshida
T
T
D000818:Animals; D001516:Bees; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D012911:Snakes; D013045:Species Specificity; D013050:Spectrometry, Fluorescence; D014966:Xanthenes / Q000302:isolation & purification / Q000494:pharmacology*
D007783:Lactones; D014966:Xanthenes; C072738:thielocin A1beta; C073571:cinatrin C3; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine