Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase

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DOI	Resolve DOI: https://doi.org/10.1021/bi701584v
Author	Search for: Epand, Richard M.; Search for: Shulga, Yulia V.; Search for: Timmons, Heath C.; Search for: Perri, Alexandra L.; Search for: Belani, Jitendra D.; Search for: Perinpanathan, Kirishanth; Search for: Johnson-McIntire, Laura Beth; Search for: Bajjalieh, Sandra; Search for: Dicu, Armela O.; Search for: Elias, Cynthia¹; Search for: Rychnovsky, Scott D.; Search for: Topham, Matthew K.
Name affiliation	National Research Council of Canada. NRC Biotechnology Research Institute
Format	Text, Article
Journal title	Biochemistry
ISSN	0006-2960 1520-4995
Volume	46
Issue	49
Pages	14225–14231
Abstract	The α, ζ, and ε isoforms of diacylglycerol kinase exhibit a high degree of stereospecificity in the phosphorylation of diacylglycerol. In comparison, a multiple lipid kinase, MuLK, shows much less stereospecificity, phosphorylating 1,2-dioleoylglycerol only ∼2−3 times more rapidly than 2,3-dioleoylglycerol. The α and ζ isoforms of diacylglycerol kinase are inhibited by 2,3-dioleoylglycerol, but not the more substrate-selective ε isoform. The inhibition by 2,3-dioleoylglycerol is uncompetitive. This corresponds to a kinetic scheme in which the inhibitor can bind to the enzyme−substrate complex, but not to the free enzyme. Our data indicate that despite their similar structures, 1,2-dioleoylglycerol and 2,3-dioleoylglycerol do not compete for the active site of these three isoforms of diacylglycerol kinase. We suggest that the 2,3-dioleoylglycerol binds to a site on the α and ζ isoforms of diacylglycerol kinase that is exposed as a consequence of the substrate binding to the active site. The chiral specificity of these enzymes thus mimics the substrate specificity, with MuLK being the least selective and the ε isoform of diacylglycerol kinase exhibiting the greatest selectivity.
Publication date	2007-11-16
Publisher	American Chemical Society
Language	English
Peer reviewed	Yes
NRC number	NRC-BRI-47820
NPARC number	3538690
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Record identifier	1aac8f58-0d85-486d-857c-db0baa900726
Record created	2009-03-01
Record modified	2020-05-27

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Date modified:: 2020-09-21