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

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.

Calibration of the dianionic phosphate group: Validation on the recognition site of the homodimeric enzyme phosphoglucose isomerase

“…The dianionic phosphate group (DPG) is ubiquitous in biochemical processes. It is the terminal end of various DNA and RNA nucleotides and several coenzymes including adenosine and guanosine di‐ and triphosphates (ADP, ATP, GDP, GTP), thiamine diphosphate (ThDP), pyridoxal phosphate (PLP) and nicotinamide adenine dinucleotide phosphate (NADPH) . Numerous proteins in their lifetimes become phosphorylated/dephosphorylated at Tyr, Ser, Thr, and His side‐chains .…”

The molecular basis of thioalcohol production in human body odour

“…Mutation of key conserved PLP and LCS interacting residues reduced activity both in vitro and in vivo (Figs. 4E and 5D, E), demonstrating their important roles in binding and catalysis 24 . Supplementary Information Table S4 summarises the steady state kinetics for all ShPatB mutants analysed for Cys-3M3SH in vitro biotransformation.…”

“…A peak in this range typically indicates the presence of a PLP intermediate and is observed in cystathionine β-lyases 23 Figure S6C). In the course of a typical PLP-DE catalysed reaction, upon substrate binding, the ε-amino group of the amino acid substrate displaces the lysine residue from the PLP to form an external aldimine [24][25][26] (Supplementary Information Figure S8). The PLP and the α-amino group of the displaced lysine next facilitate electron pair and proton shuttling that lead to breakage of the C-S bond and release of 3M3SH (see Supplementary Information Figure S8 for suggested mechanism).…”

“…While the reaction mechanism of PLP-DEs action is well established, determining the substrate specificity of novel PLP-DEs remains a major challenge 24 . To gain insights into ShPatB selectivity we modelled the structure of the external aldimine form of the enzyme bound to Cys-3M3SH.…”

Seminal plasma vitamin B 6 levels in men with asthenozoospermia and men with normal sperm motility, a measurement using liquid chromatography with tandem mass spectrometry

“…Vitamin B 6 (4,5‐bis(hydroxymethyl)‐2‐methylpyridin‐3‐ol), also named pyridoxine, refers to a group of water‐soluble essential nutrients known as B vitamins (Eshak, Iso, Muraki, & Tamakoshi, 2019). In the body, the commonly known biologically active form of vitamin B 6 is pyridoxal 5′‐phosphate, which serves as a coenzyme for a wide range of metabolic enzymes (>100 enzyme) involved, specifically, in glucose, amino acids and lipid metabolism (Liang, Han, Tan, Ding, & Li, 2019; Walden et al, 2019).…”