Biochemical and Proteomic Studies of Human Pyridoxal 5′-Phosphate-Binding Protein (PLPBP)

Fux, Anja; Sieber, Stephan A.

doi:10.1021/acschembio.9b00857

Cited by 20 publications

(13 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While all available crystal structures are consistent with PLPBP family members being monomers, size-exclusion chromatography of human PLPHP, performed in two different studies [ 23 , 36 ] revealed a second peak corresponding to dimers. In [ 23 ], the minor peak was shown to depend on disulfide bridges, a result interpreted as PLPHP being mainly monomeric with the possibility of stable dimerization via the formation of a disulfide bridge between exposed cysteines.…”

Section: Structural and Functional Features Of Plpbpsmentioning

confidence: 75%

“…Consistent with this, human mutation Tyr69Cys increased dimer formation ( Table 2 ). However, Fux and Sieber [ 36 ] challenged this view, reporting that their PLPHP preparation was predominantly dimeric even under reducing conditions [ 36 ]. They also suggested that discrepancies with the previous work may be due to differences in expression strains or purification strategies.…”

Section: Structural and Functional Features Of Plpbpsmentioning

confidence: 99%

“…As already indicated, most mutations decreased the binding of the PLP cofactor, protein levels, and/or thermal stability. That is the case for mutations Pro40Leu, Tyr69Cys, Pro87Leu, Arg205Gln, Leu175Pro and Arg241Gln [ 22 , 23 ], Arg41Gln, Val45Asp and Glu67Lys [ 36 ] and Ile94Phe, Thr116Ile and Gly224Ala [ 43 ]. It is worth noting that although Pro87 is a variable residue, the restriction in chain stereochemistry imposed by the imino acid nature of proline explains the frequently drastic structural effects resulting from proline substitutions.…”

Section: Plpbp-related Phenotypesmentioning

confidence: 99%

“…Co-immunoprecipitation with PLPHP after the crosslinking of proteins from a human embryonic kidney cell line (HEK293) revealed the presence of PLPHP in both the cytosol and mitochondria [ 36 ]. Contrary to the author’s expectations, an overrepresentation of PLP-dependent enzymes was not observed.…”

Section: Guilty By Association Strategies To Get Insights Into Plpbp ...mentioning

confidence: 99%

“…Another study investigated the effect of PLPBP inactivation on the proteome of the HEK293 cell line, which resulted in the significant upregulation of proteins associated with cytoskeleton organization and cell division as well as downregulation of two PLP-dependent enzymes involved in H 2 S synthesis [ 36 ].…”

Section: Regulation Of Gene Expression By Plpbpmentioning

confidence: 99%

See 4 more Smart Citations

The Conserved Family of the Pyridoxal Phosphate-Binding Protein (PLPBP) and Its Cyanobacterial Paradigm PipY

Tremiño

Llop

Rubio

et al. 2022

Life

View full text Add to dashboard Cite

The PLPBP family of pyridoxal phosphate-binding proteins has a high degree of sequence conservation and is represented in all three domains of life. PLPBP members, of which a few representatives have been studied in different contexts, are single-domain proteins with no known enzymatic activity that exhibit the fold type III of PLP-holoenzymes, consisting in an α/β barrel (TIM-barrel), where the PLP cofactor is solvent-exposed. Despite the constant presence of cofactor PLP (a key catalytic element in PLP enzymes), PLPBP family members appear to have purely regulatory functions affecting the homeostasis of vitamin B6 vitamers and amino/keto acids. Perturbation of these metabolites and pleiotropic phenotypes have been reported in bacteria and zebrafish after PLPBP gene inactivation as well as in patients with vitamin B6-dependent epilepsy that results from loss-of-function mutations at the PLPBP. Here, we review information gathered from diverse studies and biological systems, emphasizing the structural and functional conservation of the PLPBP members and discussing the informative nature of model systems and experimental approaches. In this context, the relatively high level of structural and functional characterization of PipY from Synechococcus elongatus PCC 7942 provides a unique opportunity to investigate the PLPBP roles in the context of a signaling pathway conserved in cyanobacteria.

show abstract

Section: Structural and Functional Features Of Plpbpsmentioning

confidence: 75%

Section: Structural and Functional Features Of Plpbpsmentioning

confidence: 99%

Section: Plpbp-related Phenotypesmentioning

confidence: 99%

Section: Guilty By Association Strategies To Get Insights Into Plpbp ...mentioning

confidence: 99%

Section: Regulation Of Gene Expression By Plpbpmentioning

confidence: 99%

See 3 more Smart Citations

The Conserved Family of the Pyridoxal Phosphate-Binding Protein (PLPBP) and Its Cyanobacterial Paradigm PipY

Tremiño

Llop

Rubio

et al. 2022

Life

View full text Add to dashboard Cite

show abstract

The ubiquitous pyridoxal 5′‐phosphate‐binding protein is also an RNA‐binding protein

Graziani,

Barile,

Parroni

et al. 2024

Protein Science

View full text Add to dashboard Cite

The pyridoxal 5′‐phosphate binding protein (PLP‐BP) is believed to play a crucial role in PLP homeostasis, which may explain why it is found in living organisms from all kingdoms. Escherichia coli YggS is the most studied homolog, but human PLP‐BP has also attracted much attention because variants of this protein are responsible for a severe form of B6‐responsive neonatal epilepsy. Yet, how PLP‐BP is involved in PLP homeostasis, and thus what its actual function is in cellular metabolism, is entirely unknown. The present study shows that YggS binds RNA and that the strength of this interaction is modulated by PLP. A key role in RNA binding is clearly played by Lys137, an invariant residue located on a protein loop away from the PLP binding site, whose importance has been highlighted previously. The interaction with RNA is evidently conserved, since it is also observed with human PLP‐BP. The RNA binding site, which is apparently located at the entrance of the PLP‐binding site, is also evolutionarily conserved. It is therefore reasonable to assume that PLP, by defining the conformation of the protein, determines the RNA binding affinity. RNA‐seq analysis of RNA co‐purified with or captured by YggS revealed SsrA and RnpB RNAs, respectively involved in trans‐translation and tRNA maturation, as the major molecular components. This work opens up new horizons for the function of the PLP‐BP, which could be related to its interaction with RNA and modulated by PLP, and thus play a role in an as yet unknown regulatory mechanism.

show abstract

Disorders of Thiamine and Pyridoxine Metabolism

Brown

Plecko

2022

Inborn Metabolic Diseases

View full text Add to dashboard Cite

Biochemical and Proteomic Studies of Human Pyridoxal 5′-Phosphate-Binding Protein (PLPBP)

Cited by 20 publications

References 57 publications

The Conserved Family of the Pyridoxal Phosphate-Binding Protein (PLPBP) and Its Cyanobacterial Paradigm PipY

The Conserved Family of the Pyridoxal Phosphate-Binding Protein (PLPBP) and Its Cyanobacterial Paradigm PipY

The ubiquitous pyridoxal 5′‐phosphate‐binding protein is also an RNA‐binding protein

Disorders of Thiamine and Pyridoxine Metabolism

Contact Info

Product

Resources

About