Vitamin B6 salvage enzymes: Mechanism, structure and regulation

Salvo, Martino L. di; Contestabile, Roberto; Safo, Martin K.

doi:10.1016/j.bbapap.2010.12.006

Cited by 199 publications

(190 citation statements)

References 101 publications

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“…In bacterial organisms (e.g. E. coli) [8], PLP can be synthesized from other B 6 vitamers. Thus, it may be expected that, in the presence of any B 6 vitamer, pdxST expression may not be required and therefore all B 6 vitamers may function as PdxR effector molecules.…”

Section: Discussion Bcpdxr Acts As Cellular Sensor Of Plpmentioning

confidence: 99%

“…However, because PLP is a very reactive aldehyde that rapidly combines with amino and thiol groups of proteins, high concentrations of this cofactor would have toxic effects [9]. Despite the importance of vitamin B 6 metabolism, only a few studies have focused on the regulation of vitamin B 6 biosynthesis and recycling [8] and, in particular, very little is known about the regulation of gene expression. Recently, the role of the transcriptional regulator PdxR in the expression of pdxST genes was analyzed in Corynebacterium glutamicum [10], Streptococcus pneumoniae [11] and Listeria monocytogenes [12].…”

Section: Introductionmentioning

confidence: 99%

“…Many bacteria (e.g. E. coli) and also organisms (such as mammalians) that are not capable of synthesizing PLP are able to recycle PLP from other B 6 vitamers contained in nutrients through the action of pyridoxal kinase and pyridoxine (pyridoxamine) 5 0 -phosphate oxidase [8]. PLP concentration in the cell needs to be finely controlled.…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B₆ biosynthesis in the probiotic bacterium Bacillus clausii

et al. 2015

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Pyridoxal 5′‐phosphate (PLP), the well‐known active form of vitamin B6, is an essential enzyme cofactor involved in a large number of metabolic processes. PLP levels need to be finely tuned in response to cell requirements; however, little is known about the regulation of PLP biosynthesis and recycling pathways. The transcriptional regulator PdxR activates transcription of the pdxST genes encoding PLP synthase. It is characterized by an N‐terminal helix‐turn‐helix motif that binds DNA and an effector‐binding C‐terminal domain homologous to PLP‐dependent enzymes. Although it is known that PLP acts as an anti‐activator, the mechanism of action of PdxR is unknown. In the present study, we analyzed the biochemical and DNA‐binding properties of PdxR from the probiotic Bacillus clausii. Spectroscopic measurements showed that PLP is the only B6 vitamer that acts as an effector molecule of PdxR. Binding of PLP to PdxR determines a protein conformational change, as detected by gel filtration chromatography and limited proteolysis experiments. We showed that two direct repeats and one inverted repeat are present in the DNA promoter region and PdxR is able to bind DNA fragments containing any combination of two of them. However, when PLP binds to PdxR, it modifies the DNA‐binding properties of the protein, making it selective for inverted repeats. A molecular mechanism is proposed in which the two different DNA binding modalities of PdxR determined by the presence or absence of PLP are responsible for the control of pdxST transcription.

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Section: Discussion Bcpdxr Acts As Cellular Sensor Of Plpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B₆ biosynthesis in the probiotic bacterium Bacillus clausii

et al. 2015

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“…It is therefore suggested that high homocysteine concentrations may have direct neurotoxic effects, resulting in apoptosis and possibly impairing pathways associated with cognition (64,83) . In addition, optimal B 6 status plays an important role in brain health through its essential role in transamination and decarboxylation reactions required for the metabolism of several neurotransmitters, including serotonin, γ-aminobutyric acid, dopamine, noradrenaline and histamine (84) .…”

Section: Potential Mechanisms Linking B-vitamins With Brain Healthmentioning

confidence: 99%

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

et al. 2014

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Nutrition plays a fundamental role in supporting the structural and functional development of the human brain from conception, throughout early infancy and extending into later life. A growing body of evidence suggests that folate and the metabolically related B-vitamins are essential for brain health across all age groups, owing to their specific roles in C 1 metabolism and particularly in the production of S-adenosylmethionine, a universal methyl donor essential for the production of neurotransmitters. Emerging, though not entirely consistent, evidence suggests that maternal folate status throughout pregnancy may influence neurodevelopment and behaviour of the offspring. Furthermore optimal B-vitamin status is associated with better cognitive health in ageing. Of note, a recent clinical trial provided evidence that supplementation with folic acid and related B-vitamins over a 2-year-period reduced global and regional brain atrophy, as measured by MRI scan in older adults. In terms of potential mechanisms, the effects of these B-vitamins on cognitive health may be independent or may be mediated by nutrient-nutrient and/or relevant gene-nutrient interactions. Furthermore, a new area of research suggests that the in utero environment influences health in later life. Folate, an important cofactor in C 1 metabolism, is indirectly involved in DNA methylation, which in turn is considered to be one of the epigenetic mechanisms that may underlie fetal programming and brain development. The present review will explore the evidence that supports a role for folate and the related B-vitamins in brain health across the lifecycle, and potential mechanisms to explain such effects.

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“…More recently, a role of PNPO in intracellular recycling of cofactor degraded enzymes 18 and channeling of PLP to its various apoenzymes has been described. 19 In order to protect cells from PLP toxicity, PLP has a strong inhibitory effect on PNPO activity. 20 The observed status epilepticus in 2 patients homozygous for the novel p.Arg225His mutation suggests that the PNPO protein carrying the mutation p.Arg225His might be completely inhibited by the administration of PLP.…”

Section: Expression Studies In Cho-k1 Cell Lines (Laboratory Ofmentioning

confidence: 99%

Pyridoxine responsiveness in novel mutations of the PNPO gene

et al. 2014

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Vitamin B6 salvage enzymes: Mechanism, structure and regulation

Cited by 199 publications

References 101 publications

Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B₆ biosynthesis in the probiotic bacterium Bacillus clausii

Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B₆ biosynthesis in the probiotic bacterium Bacillus clausii

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

Pyridoxine responsiveness in novel mutations of the PNPO gene

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Vitamin B6 salvage enzymes: Mechanism, structure and regulation

Cited by 199 publications

References 101 publications

Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B6 biosynthesis in the probiotic bacterium Bacillus clausii

Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B6 biosynthesis in the probiotic bacterium Bacillus clausii

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

Pyridoxine responsiveness in novel mutations of the PNPO gene

Contact Info

Product

Resources

About

Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B₆ biosynthesis in the probiotic bacterium Bacillus clausii

Molecular mechanism of PdxR – a transcriptional activator involved in the regulation of vitamin B₆ biosynthesis in the probiotic bacterium Bacillus clausii