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

Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Research Abstract Details 

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Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Abstract Text:

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,Scott D Rychnovsky,Matthew K Topham,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,Scott D Rychnovsky,Matthew K Topham,

The alpha, zeta, and epsilon 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 approximately 2-3 times more rapidly than 2,3-dioleoylglycerol. The alpha and zeta isoforms of diacylglycerol kinase are inhibited by 2,3-dioleoylglycerol, but not the more substrate-selective epsilon 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 alpha and zeta 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 epsilon isoform of diacylglycerol kinase exhibiting the greatest selectivity.

Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Publishing Authors By Initials

RM Epand,YV Shulga,HC Timmons,AL Perri,JD Belani,K Perinpanathan,LB Johnson-McIntire,S Bajjalieh,AO Dicu,C Elias,SD Rychnovsky,MK Topham,RM Epand,YV Shulga,HC Timmons,AL Perri,JD Belani,K Perinpanathan,LB Johnson-McIntire,S Bajjalieh,AO Dicu,C Elias,SD Rychnovsky,MK Topham,

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Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 14225-31

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 16

MONTH: 11

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 370623

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Grant and Affiliation Information for Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase.

AFFILIATION: Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. epand@mcmaster.ca

Country: United States

AGENCY: United States NCI

GRANT: CA95463

ACRONYM: CA

MEDLINETA: Biochemistry

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