Investigation on potential enzyme toxicity of clenbuterol to trypsin
Investigation on potential enzyme toxicity of clenbuterol to trypsin
复制标题
克仑特罗对胰蛋白酶潜在酶毒性的研究
DOI：
10.1016/j.saa.2012.12.017
复制
发表时间：
2013-03-15
影响因子：
4.4
通讯作者：
Liu, Rutao
中科院分区：
文献类型：
--
作者：
Chai, Jun;Xu, Qifei;Liu, Rutao
克伦特罗（CLB）是一种β 2-肾上腺素能激动剂，目前被非法用作饲料添加剂。采用多光谱技术和分子模拟方法研究了CLB与胰蛋白酶的体外毒性相互作用。CLB与胰蛋白酶在S1口袋中结合，形成以氢键为主的复合物。结合常数在289 K和310 K分别为1.79887 x 10（5）L mol（-1）和0.32584 x 10（5）L mol（-1）。随着氨基酸残基微环境的改变，胰蛋白酶的骨架变得疏松展开。胰蛋白酶的二级和三级结构也发生了变化。分子模拟研究阐明了结合信息的具体显示，并解释了大多数实验现象。CLB的结合位点导致胰蛋白酶的荧光猝灭和酶活性的抑制。结果表明，CLB对胰蛋白酶的结构和功能均有潜在的毒性作用，且随着CLB浓度的增加，毒性作用增强。(C)2012爱思唯尔有限公司版权所有。
Clenbuterol (CLB) is a kind of beta 2-adrenergic agonists which was illegally used as feed additives nowadays. The toxic interaction of CLB with trypsin, an important digestive enzyme, was studied in vitro using multi-spectroscopic methods and molecular modeling methods. CLB was proved to bind with trypsin in S1 pocket, forming a complex driven by the dominant force of H-bond. The binding constant was calculated to be 1.79887 x 10(5) L mol(-1) at 289 K and 0.32584 x 10(5) L mol(-1) at 310 K, respectively. The skeleton of trypsin became loosened and unfolded with the amino residues microenvironment changed. The secondary and tertiary structure of trypsin also varied. Molecular modeling studies illustrated specific display of the binding information and explained most of the experiment phenomena. The binding site of CLB induced the fluorescence quenching as well as inhibition of enzyme activity of trypsin. The study confirmed that CLB had potential toxicity on both the structure and function of trypsin and the effects enhanced with the increasing concentration of CLB. (C) 2012 Elsevier B.V. All rights reserved.