Protein myristoylation in health and disease.
Protein myristoylation in health and disease.
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DOI：
10.1007/s12154-009-0032-8
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发表时间：
2010-03-01
期刊：
影响因子：
--
通讯作者：
Tate, Edward W
中科院分区：
文献类型：
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作者：
Wright, Megan H;Heal, William P;Tate, Edward W
N-肉豆蔻酰化是指在真核生物中普遍存在的必需酶N-肉豆蔻酰转移酶（NMT）催化下，将14碳脂肪酸肉豆蔻酸酯连接到靶蛋白的N-末端甘氨酸残基上。NMT的许多靶蛋白是信号传导途径的重要组成部分，肉豆蔻酰化通常促进膜结合，这对适当的蛋白定位或生物功能至关重要。NMT是真菌或寄生原生动物引起的人类机会性感染的有效治疗靶点。此外，NMT涉及致癌作用，特别是结肠癌，其中有证据表明其在肿瘤形成的早期阶段上调。然而，直到最近，在所有生物体中豆蔻酰化的研究一直受到豆蔻酰化蛋白的检测和鉴定技术的缺乏的阻碍。在这里，我们介绍了N-豆蔻酰化和NMT的化学和生物学，并讨论了化学蛋白质组学技术的新发展，这些技术正在迎接研究生命系统中这种重要的共翻译修饰的挑战。
N-myristoylation is the attachment of a 14-carbon fatty acid, myristate, onto the N-terminal glycine residue of target proteins, catalysed by N-myristoyltransferase (NMT), a ubiquitous and essential enzyme in eukaryotes. Many of the target proteins of NMT are crucial components of signalling pathways, and myristoylation typically promotes membrane binding that is essential for proper protein localisation or biological function. NMT is a validated therapeutic target in opportunistic infections of humans by fungi or parasitic protozoa. Additionally, NMT is implicated in carcinogenesis, particularly colon cancer, where there is evidence for its upregulation in the early stages of tumour formation. However, the study of myristoylation in all organisms has until recently been hindered by a lack of techniques for detection and identification of myristoylated proteins. Here we introduce the chemistry and biology of N-myristoylation and NMT, and discuss new developments in chemical proteomic technologies that are meeting the challenge of studying this important co-translational modification in living systems.