Specific inhibitions of annonaceous acetogenins on class II 3-hydroxy-3-methylglutaryl coenzyme A reductase from Streptococcus pneumoniae
Specific inhibitions of annonaceous acetogenins on class II 3-hydroxy-3-methylglutaryl coenzyme A reductase from Streptococcus pneumoniae
复制标题
番荔枝苷对肺炎链球菌 II 类 3-羟基-3-甲基戊二酰辅酶 A 还原酶的特异性抑制
DOI：
10.1016/j.bmc.2011.04.019
复制
发表时间：
2011-06-01
影响因子：
3.5
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Feng, Lingling;Zhou, Li;Li, Jun
3-羟基-3-甲基戊二酰辅酶A还原酶（Class II HMGR）是一个潜在的靶点，可用于寻找抗肺炎链球菌侵袭性疾病的药物。然而，到目前为止还没有发现II类HMGR的强效抑制剂。首次研究了4种番荔枝内酯类化合物对番茄溃疡病菌的抑制作用。pneumoniae HMGR。结果表明，ACG对S.与I类HMGR的经典抑制剂他汀类药物洛伐他汀（Ki = 116.25 μ M）相比，K-i值在6.45-20.49 μ M的范围内。通过三维建模和对接仿真分析了ACG与S的可能结合方式。pneumoniae HMGR的结构和结合模式，为设计靶向酶S. pneumoniae HMGR的抑制剂提供了一种新的结构和结合模式。pneumoniae II HMGR。(C)2011爱思唯尔有限公司保留所有权利。
3-Hydroxy-3-methylglutaryl coenzyme A reductase (class II HMGR) could serve as a potential target to discover drugs fighting against the invasive diseases originated from Streptococcus pneumoniae, one of the major causes of bacterial disease in human. However, no strongly effective inhibitors of class II HMGR have been found so far. In the present study, for the first time, four annonaceous acetogenins (ACGs) were explored for the inhibition on S. pneumoniae HMGR. The results showed that the ACGs had higher inhibitory activities against S. pneumoniae HMGR with K-i values in the range of 6.45-20.49 mu M than the statin drug lovastatin (K-i = 116.25 mu M), a classical inhibitor of class I HMGR. Then, three-dimensional modeling and docking simulations analyzed the possible binding mode of ACGs to S. pneumoniae HMGR and suggested a kind of novel structural and binding mode for designing promising inhibitor candidates of the targeted enzyme S. pneumoniae II HMGR. (C) 2011 Elsevier Ltd. All rights reserved.