HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fierke, C. A. Articles by Jencks, W. P. Search for Related Content PubMed PubMed Citation Articles by Fierke, C. A. Articles by Jencks, W. P. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 261, Issue 17, 7603-7606, 06, 1986

Two functional domains of coenzyme A activate catalysis by coenzyme A transferase. Pantetheine and adenosine 3'-phosphate 5'-diphosphate

CA Fierke and WP Jencks

Studies of the reactivity of succinyl-CoA:3-keto acid CoA transferase with a small coenzyme A analog, methylmercaptopropionate, have shown that noncovalent interactions between the enzyme and the side chain of CoA are responsible for a rate acceleration of approximately 10(12), which is close to the total rate acceleration brought about by the enzyme (Moore, S. A., and Jencks, W. P. (1982) J. Biol. Chem. 257, 10893-10907). We report here that interaction between the enzyme and the pantetheine moiety of CoA provides the majority of the rate acceleration and destabilization of the enzyme-thiol ester intermediate that is observed with CoA substrates. The role of the adenosine 3'- phosphate 5'-diphosphate moiety of CoA is to provide 6.9 kcal/mol of binding energy in order to pull the pantetheine moiety into the active site. The enzyme-thiol ester intermediate, E-pantetheine, was generated by reaction of pantetheine with the thiol ester of enzyme and methylmercaptopropionate. E-Pantetheine undergoes hydrolysis with khyd = 2 min-1, 140-fold faster than E-CoA, and reacts with acetoacetate with kAcAc = 3 X 10(6) M-1 min-1, only 10-fold slower than E-CoA. However, in the reverse direction acetoacetylpantetheine reacts with CoA transferase (kAcAc-SP = 220 M-1 min-1) 1.6 X 10(6) times slower than acetoacetyl-CoA. The equilibrium constant for the reaction of pantetheine with E-CoA is approximately 8 X 10(-6).
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. S. Rangarajan, Y. Li, E. Ajamian, P. Iannuzzi, S. D. Kernaghan, M. E. Fraser, M. Cygler, and A. Matte Crystallographic Trapping of the Glutamyl-CoA Thioester Intermediate of Family I CoA Transferases J. Biol. Chem., December 30, 2005; 280(52): 42919 - 42928. [Abstract] [Full Text] [PDF]

				S. Benkovic, C. Fierke, and A. Naylor Insights into enzyme function from studies on mutants of dihydrofolate reductase Science, March 4, 1988; 239(4844): 1105 - 1110. [Abstract] [PDF]

				S.A. Benner, R.K. Allemann, A.D. Ellington, L. Ge, A. Glasfeld, G.F. Leanz, T. Krauch, L.J. MacPherson, S. Moroney, J.A. Piccirilli, et al. Natural Selection, Protein Engineering, and the Last Riboorganism: Rational Model Building in Biochemistry Cold Spring Harb Symp Quant Biol, January 1, 1987; 52(0): 53 - 63. [Abstract] [PDF]

				W.P. Jencks Economics of Enzyme Catalysis Cold Spring Harb Symp Quant Biol, January 1, 1987; 52(0): 65 - 73. [Abstract] [PDF]