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Review
. 2011 Nov;1814(11):1419-25.
doi: 10.1016/j.bbapap.2010.12.007. Epub 2010 Dec 20.

The PLP cofactor: lessons from studies on model reactions

John P Richard  1 , Tina L Amyes, Juan Crugeiras, Ana Rios
Affiliations
Review

The PLP cofactor: lessons from studies on model reactions

John P Richard et al. Biochim Biophys Acta. 2011 Nov.

Abstract

Experimental probes of the acidity of weak carbon acids have been developed and used to determine the carbon acid pK(a)s of glycine, glycine derivatives and iminium ion adducts of glycine to the carbonyl group, including 5'-deoxypyridoxal (DPL). The high reactivity of the DPL-stabilized glycyl carbanion towards nucleophilic addition to both DPL and the glycine-DPL iminium ion favors the formation of Claisen condensation products at enzyme active sites. The formation of the iminium ion between glycine and DPL is accompanied by a 12-unit decrease in the pK(a) of 29 for glycine. The complicated effects of formation of glycine iminium ions to DPL and other aromatic and aliphatic aldehydes and ketones on carbon acid pK(a) are discussed. These data provide insight into the contribution of the individual pyridine ring substituents to the catalytic efficiency of DPL. It is suggested that the 5'-phosphodianion group of PLP may play an important role in enzymatic catalysis of carbon deprotonation by providing up to 12 kcal/mol of binding energy that is utilized to stabilize the transition state for the enzymatic reaction. This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology.

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Figures

Figure 1
Figure 1
Profiles that show the changes in free energy for deprotonation of weak carbon acids (eq 1) to form carbanion products. Note that the barrier to thermodynamically unfavorable proton transfer (ΔG†HO) is equal to the sum of the thermodynamic barriers to proton transfer (ΔG°) and the barrier to downhill protonation of the carbanion in the reverse direction (ΔG†HOH). (A) Strongly thermodynamically unfavorable proton transfer reaction, for which there is a limiting small barrier to protonation of the carbanion by water. (B) Thermodynamically unfavorable formation of a strongly resonance stabilized carbanion, for which there is a substantial kinetic barrier to protonation of the carbanion by water [61].
Scheme 1
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Scheme 5
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Scheme 6
Chart 1
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Chart 3
See this image and copyright information in PMC

References

    1. Toney MD. The chemistry of PLP-dependent enzymes. Wiley Encyclopedia of Chemical Biology. 2009;3:731–735.
    1. Toney MD. Reaction specificity in pyridoxal phosphate enzymes. Arch Biochem Biophys. 2005;433:279–287. - PubMed
    1. Richard JP, Amyes TL. On the importance of being zwitterionic: enzymic catalysis of decarboxylation and deprotonation of cationic carbon. Bioorg Chem. 2004;32:354–366. - PubMed
    1. Richard JP, Amyes TL, Crugeiras J, Rios A. Pyridoxal 5′-phosphate: electrophilic catalyst extraordinaire. Curr Opin Chem Biol. 2009;13:475–483. - PMC - PubMed
    1. Dunathan HC. Conformation and reaction specificity in pyridoxal phosphate enzymes. Proc Nat Acad Sci. 1966;55:712–716. - PMC - PubMed

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