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Review
. 2011 Nov;1814(11):1407-18.
doi: 10.1016/j.bbapap.2011.05.019. Epub 2011 Jun 6.

Controlling reaction specificity in pyridoxal phosphate enzymes

Michael D Toney  1
Affiliations
Review

Controlling reaction specificity in pyridoxal phosphate enzymes

Michael D Toney. Biochim Biophys Acta. 2011 Nov.

Abstract

Pyridoxal 5'-phosphate enzymes are ubiquitous in the nitrogen metabolism of all organisms. They catalyze a wide variety of reactions including racemization, transamination, decarboxylation, elimination, retro-aldol cleavage, Claisen condensation, and others on substrates containing an amino group, most commonly α-amino acids. The wide variety of reactions catalyzed by PLP enzymes is enabled by the ability of the covalent aldimine intermediate formed between substrate and PLP to stabilize carbanionic intermediates at Cα of the substrate. This review attempts to summarize the mechanisms by which reaction specificity can be achieved in PLP enzymes by focusing on three aspects of these reactions: stereoelectronic effects, protonation state of the external aldimine intermediate, and interaction of the carbanionic intermediate with the protein side chains present in the active site. This article is part of a Special Issue entitled: Pyridoxal Phosphate Enzymology.

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Figures

Figure 1
Figure 1
Variety of reactions catalyzed by PLP. Several other reaction types are not shown for clarity.
Figure 2
Figure 2
Resonance structures of carbanionic intermediates. The quinonoid structure is shown on the right.
Figure 3
Figure 3
PLP catalyzed racemization mechanism, and the active site structure of alanine racemase with PPL-L-Ala (reduced Schiff base) bound.
Figure 4
Figure 4
PLP catalyzed transamination mechanism, and the active site structure of AAT with PPL-L-Asp (reduced Schiff base) bound.
Figure 5
Figure 5
Stereoelectronic effects in the external aldimine intermediate. The alignment of a particular bond with the p orbitals of the conjugated π system selectively labilizes it through GS (hyperconjugative) and TS (resonance) effects.
Figure 6
Figure 6
Mechanism for the DGD catalyzed oxidative decarboxylation of 2,2-dialkylglycines and transamination of alanine/pyruvate.
Figure 7
Figure 7
(A) Active site structure of DGD. (B) Schematic of the DGD active site showing the locations of the A, B, and C binding subsites.
Figure 8
Figure 8
Isotopic free energy profiles for alanine racemase. The solid line is for protiated alanine and the dashed is for deuterated alanine.
Figure 9
Figure 9
Mechanism of aspartate β-decarboxylase, and active site structure.
See this image and copyright information in PMC

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