Role of binding energy with coenzyme A in catalysis by 3-oxoacid coenzyme A transferase

Biochemistry
A WhittyW P Jencks

Abstract

Succinyl-CoA:3-oxoacid coenzyme A transferase (EC 2.8.3.5), which catalyzes the reversible conversion of succinyl-CoA and acetoacetate into acetoacetyl-CoA and succinate through a covalent enzyme thiol ester intermediate, E-CoA, utilizes binding energy from noncovalent interactions with CoA to bring about an increase in kcat/KM of approximately 10(10)-fold. The approximately 40-fold stronger binding of desulfo-CoA (KI = 2.7 +/- 0.7 mM) compared to desulfopantetheine (KI = 110 +/- 15 mM), both of which inhibit competitively with respect to acetoacetyl-CoA, shows that binding to the nucleotide domain of CoA at the active site provides ca. -2.2 kcal/mol of binding energy to stabilize noncovalent complexes with the enzyme. This is much smaller than the ca. -8.9 kcal/mol that the nucleotide domain contributes to the stabilization of the transition state and the ca. -7.2 kcal/mol that it contributes to stabilizing the E-CoA intermediate [Fierke, C. A., & Jencks, W. P. (1986) J. Biol. Chem. 261, 7603-7606]. This shows that most of the approximately 10(6)-fold increase in kcat/KM that is brought about by binding to this domain is in kcat, which is increased by a factor of about 10(5). Binding to the central pantoic acid domain of CoA i...Continue Reading

Citations

Oct 1, 1996·Nature Structural Biology·W R CannonS J Benkovic
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jason P SchwansDaniel Herschlag
Jan 1, 1997·Annual Review of Biochemistry·W P Jencks
Apr 22, 2003·Annual Review of Biochemistry·Daniel A KrautDaniel Herschlag
Jan 19, 2013·Biochemistry·Tina L Amyes, John P Richard
Mar 5, 2013·Biochemistry·John P Richard
Oct 29, 2005·The Journal of Biological Chemistry·Erumbi S RangarajanAllan Matte
Jul 21, 2020·Chemical Reviews·Kamila B MuchowskaJoseph Moran
Sep 16, 2020·Biochemistry·Brian P CallahanXiaoyu Zhang
Feb 1, 2019·Journal of the American Chemical Society·John P Richard

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