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
中科院分区:
文献类型:
--
作者:
Ma Q;Srinivasan L;Gabelli SB;Raben DM
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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