Pyridoxal 5'-phosphate: Electrophilic Catalyst Extraordinaire

Overview

Journal Curr Opin Chem Biol

Publisher Elsevier

Specialty Biochemistry

Date 2009 Jul 31

PMID 19640775

Citations 30

Authors

John P Richard

Tina L Amyes

Juan Crugeiras

Ana Rios

Affiliations

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Abstract

Studies of nonenzymatic electrophilic catalysis of carbon deprotonation of glycine show that pyridoxal 5'-phosphate (PLP) strongly enhances the carbon acidity of alpha-amino acids, but that this is not the overriding mechanistic imperative for cofactor catalysis. Although the fully protonated PLP-glycine iminium ion adduct exhibits an extraordinary low alpha-imino carbon acidity (pK(a)=6), the more weakly acidic zwitterionic iminium ion adduct (pK(a)=17) is selected for use in enzymatic reactions. The similar alpha-imino carbon acidities of the iminium ion adducts of glycine with 5'-deoxypyridoxal and with phenylglyoxylate show that the cofactor pyridine nitrogen plays a relatively minor role in carbanion stabilization. The 5'-phosphodianion group of PLP likely plays an important role in catalysis by providing up to 12 kcal/mol of binding energy that may be utilized for transition state stabilization.

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