Elusive structure of mammalian DGKs

Qianqian Ma; Lakshmi Srinivasan; Sandra B Gabelli; Daniel M Raben

doi:10.1016/j.jbior.2021.100847

Elusive structure of mammalian DGKs

Adv Biol Regul. 2022 Jan:83:100847. doi: 10.1016/j.jbior.2021.100847. Epub 2021 Dec 2.

Authors

Qianqian Ma¹, Lakshmi Srinivasan², Sandra B Gabelli³, Daniel M Raben⁴

Affiliations

¹ Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: gabelli@jhmi.edu.
⁴ Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: draben@jhmi.edu.

Abstract

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. 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.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Diacylglycerol Kinase* / metabolism
Humans
Mammals / genetics
Mammals / metabolism
Phosphatidic Acids*
Phosphorylation
Protein Isoforms
Signal Transduction

Substances

Phosphatidic Acids
Protein Isoforms
Diacylglycerol Kinase

Grants and funding

R01 NS077923/NS/NINDS NIH HHS/United States