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

Article Details

Citation

Copy to clipboard

Fux A, Sieber SA

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

ACS Chem Biol. 2020 Jan 17;15(1):254-261. doi: 10.1021/acschembio.9b00857. Epub 2019 Dec 26.

PubMed ID

31825581 [ View in PubMed

]

Abstract

The pyridoxal 5'-phosphate-binding protein (PLPBP) is an evolutionarily conserved protein linked to pyridoxal 5'-phosphate-binding. Although mutations in PLPBP were shown to cause vitamin B6-dependent epilepsy, its cellular role and function remain elusive. We here report a detailed biochemical investigation of human PLPBP and its epilepsy-causing mutants by evaluating stability, cofactor binding, and oligomerization. In this context, chemical cross-linking combined with mass spectrometry unraveled an unexpected dimeric assembly of PLPBP. Furthermore, the interaction network of PLPBP was elucidated by chemical cross-linking paired with co-immunoprecipitation. A mass spectrometric analysis in a PLPBP knockout cell line resulted in distinct proteomic changes compared to wild type cells, including upregulation of several cytoskeleton- and cell division-associated proteins. Finally, transfection experiments with vitamin B6-dependent epilepsy-causing PLPBP variants indicate a potential role of PLPBP in cell division as well as proper muscle function. Taken together, our studies on the structure and cellular role of human PLPBP enable a better understanding of the physiological and pathological mechanism of this important protein.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pyridoxal phosphate	Proline synthase co-transcribed bacterial homolog protein	Protein	Humans	Unknown	Binder	Details