Elusive structure of mammalian DGKs.

Elusive structure of mammalian DGKs.
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DOI:
10.1016/j.jbior.2021.100847
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发表时间:
2022-01
影响因子:
--
通讯作者:
Raben DM
Raben DM
中科院分区:
其他
文献类型:
--
作者:
Ma Q;Srinivasan L;Gabelli SB;Raben DM

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哺乳动物二酰基甘油激酶(DGKs)是一组催化atp依赖性二酰基甘油(DAG)磷酸化产生磷脂酸(PtdOH)的酶。在此过程中,它们调节了这两种重要的信号脂质的水平。目前,10种哺乳动物dgk被分为5类,它们在结构域组织、调控和细胞/亚细胞分布方面各不相同。由于脂质在细胞中起着至关重要的作用,因此人们对了解脂质调节酶(如DGKs)的催化和调节机制越来越感兴趣,这并不奇怪。然而,真核生物DGKs的三维结构尚未得到解决。在这篇综述中,我们总结了在确定这些重要酶的结构方面已知的和当前的挑战。除了获得对其催化和调控机制的关键见解外,DGK结构还将为设计异构体特异性抑制剂提供平台。
Mammalian diacylglycerol kinases (DGKs) are a group of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PtdOH). In doing so, they modulate the levels of these two important signaling lipids. Currently, ten mammalian DGKs are organized into five classes that vary with respect to domain organization, regulation, and cellular/subcellular distribution (reviewed in ). As lipids play critical roles in cells, it is not surprising that there is increasing interest in understanding the mechanism underlying the catalysis and regulation of lipid modulating enzymes such as DGKs. However, there are no solved 3D structures for any of the eukaryotic DGKs. In this review, we summarize what is known and the current challenges in determining the structures of these important enzymes. In addition to gain critical insights into their mechanisms of catalysis and regulation, DGK structures will provide a platform for the design of isoform specific inhibitors.
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