通过计算机模拟的对接过程研究,发现了MS-275--一种苯甲酰胺类的组蛋白去乙酰酶(HDAC)抑制剂与酶的可能的全新结合方式.这种结合方式与已经阐明的组蛋白去乙酰酶类似蛋白(HDLP)与曲古柳菌素A(trichostatin A,TSA)和suberoylanilide hydroxamic acid(SAHA)形成的复合物晶体结构中配体与酶的作用方式完全不同.从对接结果看,MS-275的作用靶点在酶活性口袋的最狭窄部位,而不是直接作用于锌离子.这似乎能够解释MS-275的低毒性特点,并且为设计和筛选全新的HDAC抑制剂提供了新思路.%The paper proposed a possible binding mode of MS-275, a benzamide histone deacetylase(HDAC) inhibitor, to HDAC by intensive docking study. This binding mode is different from those observed in the crystal structure of complexes formed by a histone deacetylase-like protein (HDLP) with trichostatin A(TSA) or suberoylanilide hydroxamic acid (SAHA). The docking result implicates that the main target of MS-275 is the narrowest part of H-DAC active pocket. It seems to be able to explain the low toxicity of MS-275 and provides new insights on the design of novel HDAC inhibitors.
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