Current Advances on Structure-Function Relationships of Pyridoxal 5'-Phosphate-Dependent Enzymes.

Jing Liang,Yang Tan,Haizhen Ding,Qian Han,Jianyong Li

doi:10.3389/fmolb.2019.00004

Abstract

Pyridoxal 5′-phosphate (PLP) functions as a coenzyme in many enzymatic processes, including decarboxylation, deamination, transamination, racemization, and others. Enzymes, requiring PLP, are commonly termed PLP-dependent enzymes, and they are widely involved in crucial cellular metabolic pathways in most of (if not all) living organisms. The chemical mechanisms for PLP-mediated reactions have been well elaborated and accepted with an emphasis on the pure chemical steps, but how the chemical steps are processed by enzymes, especially by functions of active site residues, are not fully elucidated. Furthermore, the specific mechanism of an enzyme in relation to the one for a similar class of enzymes seems scarcely described or discussed. This discussion aims to link the specific mechanism described for the individual enzyme to the same types of enzymes from different species with aminotransferases, decarboxylases, racemase, aldolase, cystathionine β-synthase, aromatic phenylacetaldehyde synthase, et al. as models. The structural factors that contribute to the reaction mechanisms, particularly active site residues critical for dictating the reaction specificity, are summarized in this review.

Highlights

Pyridoxal 5′-phosphate (PLP) is one of the active forms of vitamin B6, which is produced by pyridoxal kinase-mediated reactions
The ε-amino group of the lysine residue and the aldehyde group of PLP forms a Schiff-base structure. Because this Schiff-base structure is linked through a protein-associated lysine residue, it is commonly referred as internal aldimine
In addition to uncharged aromatic amino acid for π-π stacking with PLP, there are two active site residues Asn and Tyr that are conserved in aminotransferases (Figure 2) and form hydrogen bonds with PLP phenol group O3′ (Figure 2) (Sivaraman et al, 2001; Han et al, 2008a,b, 2010a,b; Duff et al, 2012; Nasir et al, 2016)

Summary

Introduction

Pyridoxal 5′-phosphate (PLP) is one of the active forms of vitamin B6, which is produced by pyridoxal kinase-mediated reactions. PLP-dependent enzymes catalyze a wide variety of reaction types and usually have a conserved lysine residue in the active site for PLP binding.

Results

Conclusion