Titration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N-myristoyltransferase

Biochemistry
R S BhatnagarJ I Gordon

Abstract

Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase (Nmt1p) is an essential enzyme that catalyzes the transfer of myristic acid (C14:0) from myristoylCoA to the N-terminus of cellular proteins with a variety of functions. Nmts from an assortment of species display remarkable in vivo specificity for this rare acyl chain. To better understand the mechanisms underlying this specificity, we have used isothermal titration calorimetry as well as kinetic measurements to study the interactions of Nmt1p with acylCoA analogs having variations in chain length and/or conformation, analogs with alterations in the thioester bond, and analogs with or without a 3'-phosphate in their CoA moiety. MyristoylCoA binds to Nmt1p with a Kd of 15 nM and a large exothermic deltaH (-25 kcal/mol). CoA derivatives of C12:0-C16:0 fatty acids bind to Nmt1p with similar affinity, but with much smaller deltaH and a correspondingly less negative TdeltaS than myristoylCoA. Replacing the thioester carbonyl group with a methylene or removing the 3'-phosphate of CoA is each sufficient to prevent the low enthalpy binding observed with myristoylCoA. The carbonyl and the 3'-phosphate have distinct and important roles in chain length recognition over t...Continue Reading

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Citations

Apr 22, 2008·Molecular Neurobiology·Nikolai O Artemyev
Nov 10, 2009·Journal of Chemical Biology·Megan H WrightEdward W Tate
Jul 9, 1999·Progress in Lipid Research·J C DeMarR E Anderson
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Sep 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·O Wolf Lindwasser, Marilyn D Resh
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Feb 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Markus IslingerMichael Schrader

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