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Fatty acylation of proteins: The long and the short of it
Progress in Lipid Research ( IF 13.6 ) Pub Date : 2016-05-24 , DOI: 10.1016/j.plipres.2016.05.002
Marilyn D. Resh

Long, short and medium chain fatty acids are covalently attached to hundreds of proteins. Each fatty acid confers distinct biochemical properties, enabling fatty acylation to regulate intracellular trafficking, subcellular localization, protein-protein and protein-lipid interactions. Myristate and palmitate represent the most common fatty acid modifying groups. New insights into how fatty acylation reactions are catalyzed, and how fatty acylation regulates protein structure and function continue to emerge. Myristate is typically linked to an N-terminal glycine, but recent studies reveal that lysines can also be myristoylated. Enzymes that remove N-terminal myristoyl-glycine or myristate from lysines have now been identified. DHHC proteins catalyze S-palmitoylation, but the mechanisms that regulate substrate recognition by individual DHHC family members remain to be determined. New studies continue to reveal thioesterases that remove palmitate from S-acylated proteins. Another area of rapid expansion is fatty acylation of the secreted proteins hedgehog, Wnt and Ghrelin, by Hhat, Porcupine and GOAT, respectively. Understanding how these membrane bound O-acyl transferases recognize their protein and fatty acyl CoA substrates is an active area of investigation, and is punctuated by the finding that these enzymes are potential drug targets in human diseases.



中文翻译:

蛋白质的脂肪酰化:长短

长,短和中链脂肪酸共价结合到数百种蛋白质上。每种脂肪酸都具有独特的生化特性,使脂肪酰化可以调节细胞内运输,亚细胞定位,蛋白质-蛋白质和蛋白质-脂质相互作用。肉豆蔻酸酯和棕榈酸酯代表最常见的脂肪酸修饰基团。关于脂肪酰化反应如何被催化以及脂肪酰化如何调节蛋白质结构和功能的新见解不断涌现。肉豆蔻酸酯通常与N端甘氨酸相连,但是最近的研究表明,赖氨酸也可以被肉豆蔻酰化。现已鉴定出可从赖氨酸中去除N末端肉豆蔻酰甘氨酸或肉豆蔻酸酯的酶。DHHC蛋白催化S-棕榈酰化,但是调节各个DHHC家族成员对底物识别的机制仍有待确定。新的研究继续揭示了硫酯酶可以从S-酰化的蛋白质中去除棕榈酸酯。快速扩展的另一个领域是分别由Hhat,Porcupine和GOAT对分泌的蛋白质刺猬,Wnt和Ghrelin进行脂肪酰化。了解这些膜结合的O-酰基转移酶如何识别其蛋白质和脂肪酰基CoA底物是研究的活跃领域,并且因发现这些酶是人类疾病的潜在药物靶点而被打断。分别。了解这些膜结合的O-酰基转移酶如何识别其蛋白质和脂肪酰基CoA底物是研究的活跃领域,并且因发现这些酶是人类疾病的潜在药物靶点而被打断。分别。了解这些膜结合的O-酰基转移酶如何识别其蛋白质和脂肪酰基CoA底物是研究的活跃领域,并且因发现这些酶是人类疾病的潜在药物靶点而被打断。

更新日期:2016-05-24
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