Acetyl-coenzyme A carboxylases: Versatile targets for drug discovery
Acetyl-coenzyme A carboxylases: Versatile targets for drug discovery
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DOI：
10.1002/jcb.21077
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发表时间：
2006-12-15
影响因子：
4
通讯作者：
Harwood, H. James, Jr.
中科院分区：
文献类型：
--
作者：
Tong, Liang;Harwood, H. James, Jr.
乙酰辅酶A羧化酶（ACCs）在人类和大多数其他生物的脂肪酸代谢中起着至关重要的作用。它们是针对多种人类疾病（包括糖尿病、肥胖、癌症和微生物感染）的药物发现的有吸引力的靶点。此外，从草中提取的acc是除草剂的目标，这些除草剂已经在商业上使用了20多年。近年来，对这些酶的研究在基础研究和药物开发方面都取得了重大进展。在基础研究层面，已经确定了ACC的生物素羧化酶（130）和羧化转移酶（CT）组分的晶体结构，并开始了解小分子抑制ACC的分子基础。在药物发现层面，大量哺乳动物acc的纳摩尔抑制剂已被报道，其治疗潜力的程度正在积极探索。本文对这些新进展进行了总结，并对这些重要酶的未来研究方向进行了展望。
Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in humans and most other living organisms. They are attractive targets for drug discovery against a variety of human diseases, including diabetes, obesity, cancer, and microbial infections. In addition, ACCs from grasses are the targets of herbicides that have been in commercial use for more than 20 years. Significant progresses in both basic research and drug discovery have been made over the past few years in the studies on these enzymes. At the basic research level, the crystal structures of the biotin carboxylase (130 and the carboxyltransferase (CT) components of ACC have been determined, and the molecular basis for ACC inhibition by small molecules are beginning to be understood. At the drug discovery level, a large number of nanomolar inhibitors of mammalian ACCs have been reported and the extent of their therapeutic potential is being aggressively explored. This review summarizes these new progresses and also offers some prospects in terms of the future directions for the studies on these important enzymes.