de Carvalho M S, Jacobs R S
Department of Biological Sciences, University of California, Santa Barbara 93106.
Biochem Pharmacol. 1991 Sep 27;42(8):1621-6. doi: 10.1016/0006-2952(91)90432-5.
Scalaradial (SLD), a marine natural product isolated from the sponge (Cacospongia sp., possesses anti-inflammatory properties in vivo and in vitro (Pharmacologist 32: 168, 1990). In this study we characterize its effects against bee venom phospholipase A2 (PLA2; EC 3.1.1.4). SLD is a potent inactivator of bee venom PLA2 with an IC50 value of 0.07 microM. Inactivation of bee venom PLA2 occurred in a time-dependent, irreversible manner. The rate of inactivation followed first-order reaction kinetics and was dependent on the concentration of SLD. Kinetic analysis suggested a two-step mechanism of inactivation: an initial apparent noncovalent binding (Ki = 4.5 x 10(-5) M) followed by covalent modification. The rate of inactivation was reduced markedly in the presence of excess phosphatidylcholine, suggesting that modification of the enzyme occurs at or near the substrate binding site.
Scalaradial（SLD）是一种从海绵（Cacospongia sp.）中分离出的海洋天然产物，在体内和体外均具有抗炎特性（《药理学家》32: 168, 1990）。在本研究中，我们描述了其对蜂毒磷脂酶A2（PLA2；EC 3.1.1.4）的作用。SLD是蜂毒PLA2的强效失活剂，IC50值为0.07微摩尔。蜂毒PLA2的失活以时间依赖性、不可逆的方式发生。失活速率遵循一级反应动力学，且依赖于SLD的浓度。动力学分析表明失活机制为两步：初始的明显非共价结合（Ki = 4.5×10⁻⁵ M），随后是共价修饰。在过量磷脂酰胆碱存在的情况下，失活速率显著降低，表明酶的修饰发生在底物结合位点或其附近。
