The hard-soft acid-base principle in enzymatic catalysis: dual reactivity of phosphoenolpyruvate.
In this paper, the chemical reactivity of C3 of phosphoenolpyruvate (PEP) has been analyzed in terms of density functional theory quantified through quantum chemistry calculations. PEP is involved in a number of important enzymatic reactions, in which its C3 atom behaves like a base. In three different enzymatic reactions analyzed here, C3 sometimes behaves like a soft base and sometimes behaves like a hard base in terms of the hard-soft acid-base principle. This dual nature of C3 of PEP was found to be related to the conformational change of the molecule. This leads to a testable hypothesis: that PEP adopts particular conformations in the enzyme-substrate complexes of different PEP-using enzymes, and that the enzymes control the reactivity through controlling the dihedral angle between the carboxylate and the C==C double bond of PEP.
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Department of Biochemistry and Biophysics, Washington State University, Pullman, 99164-4660, USA.
Evans
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D010723:3-Deoxy-7-Phosphoheptulonate Synthase / Q000737:chemistry / Q000378:metabolism; D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D000446:Aldehyde-Lyases / Q000737:chemistry / Q000378:metabolism; D019883:Alkyl and Aryl Transferases; D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008968:Molecular Conformation; D010728:Phosphoenolpyruvate / Q000737:chemistry* / Q000378:metabolism*; D011789:Quantum Theory; D013816:Thermodynamics; D014166:Transferases / Q000737:chemistry / Q000378:metabolism
D004798:Enzymes; D010728:Phosphoenolpyruvate; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D010723:3-Deoxy-7-Phosphoheptulonate Synthase; C020011:2-dehydro-3-deoxyphosphooctonate aldolase; D000446:Aldehyde-Lyases