Abstract
We have studied the mechanism of enzyme-catalyzed alkyl transfer reactions by a variety of methods including non-enzymic model reactions, steady-state kinetics, and stereochemistry. In this brief paper, the results of our earlier work on catechol O-methyltransferase (COMT, E.C. 2.1.1.6) and more recent work on putrescine aminopropyltransferase (PAPT, E.C. 2.5.1.16, sometimes referred to as spermidine synthase) will be reviewed. These investigations have resulted in the demonstration that each of these alkyltransferases catalyze a reaction which proceeds via a ternary complex involving the enzyme and both nucleophilic and electrophilic substrates. In addition, the demonstration of general base catalysis in related model reactions, provides chemical precedent for the involvement of this type of catalysis by basic residues of the enzyme. The mechanistic conclusions have allowed us to design and synthesize several mechanism-based inhibitors which exhibit great potency and specificity for individual alkyltransferases1.
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References
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© 1988 Plenum Press, New York
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Coward, J.K. (1988). Aminopropyltransferases: Mechanistic Studies and the Synthesis of Specific Inhibitors. In: Zappia, V., Pegg, A.E. (eds) Progress in Polyamine Research. Advances in Experimental Medicine and Biology, vol 250. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5637-0_11
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DOI: https://doi.org/10.1007/978-1-4684-5637-0_11
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