Substrate Chirality and Specificity of Diacylglycerol Kinases and the Multisubstrate Lipid Kinase

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• 作者：Richard M. Epand ; Yulia V. Shulga ; Heath C. Timmons ; Alexandra L. Perri ; Jitendra D. Belani ; Kirishanth Perinpanathan ; Laura Beth Johnson-McIntire ; Sandra Bajjalieh ; Armela O. Dicu ; Cynthia Elias ; Sco
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：December 11, 2007
• 年：2007
• 卷：46
• 期：49
• 页码：14225 - 14231
• 全文大小：128K
• 年卷期：v.46,no.49(December 11, 2007)
• ISSN：1520-4995

文摘

The , , and isoforms of diacylglycerol kinase exhibit a high degree of stereospecificity inthe phosphorylation of diacylglycerol. In comparison, a multiple lipid kinase, MuLK, shows much lessstereospecificity, phosphorylating 1,2-dioleoylglycerol only ~2-3 times more rapidly than 2,3-dioleoylglycerol. The and isoforms of diacylglycerol kinase are inhibited by 2,3-dioleoylglycerol, butnot the more substrate-selective isoform. The inhibition by 2,3-dioleoylglycerol is uncompetitive. Thiscorresponds to a kinetic scheme in which the inhibitor can bind to the enzyme-substrate complex, butnot to the free enzyme. Our data indicate that despite their similar structures, 1,2-dioleoylglycerol and2,3-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 and isoforms of diacylglycerol kinasethat is exposed as a consequence of the substrate binding to the active site. The chiral specificity of theseenzymes thus mimics the substrate specificity, with MuLK being the least selective and the isoform ofdiacylglycerol kinase exhibiting the greatest selectivity.