Phosphatidylinositol 4-kinases: Function, structure, and inhibition

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• 作者：Evzen Boura ; ^{boura@uochb.cas.cz" class="auth_mail" title="E-mail the corresponding author} ; Radim Nencka ; ^{nencka@uochb.cas.cz" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Phosphatidylinositol 4-kinase ; Inhibitor ; Crystal structure ; Virus
• 刊名：Experimental Cell Research
• 出版年：2015
• 出版时间：1 October 2015
• 年：2015
• 卷：337
• 期：2
• 页码：136-145
• 全文大小：1836 K

文摘

The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (伪 and 尾) and two type III enzymes (伪 and 尾). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.