Dataset Information

Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress

ABSTRACT: Methylglyoxal (MGO) is a highly reactive cellular metabolite that glycates lysine and arginine residues to form post-translational modifications known as advanced glycation end products. Because of their low abundance and low stoichiometry, few studies have reported their occurrence and site-specific locations in proteins. Proteomic analysis of WIL2-NS B lymphoblastoid cells in the absence and presence of exogenous MGO was conducted to investigate the extent of MGO modi-fications. We found over 500 MGO modified proteins, revealing an over-representation of these modifications on many glycolytic enzymes, as well as ribosomal and spliceosome proteins. Moreover, MGO modifications were observed on the active site residues of glycolytic enzymes that could alter their activity. We similarly observed modification of glycolytic enzymes across several epithelial cell lines and peripheral blood lymphocytes, with modification of fructose bisphosphate aldolase being observed in all samples. These results indicate that glycolytic proteins could be particularly prone to the formation of MGO adducts.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Leigh Donnellan

LAB HEAD: Permal Deo

PROVIDER: PXD032812 | Pride | 2022-05-20

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20210322_ProAlanase_0-5mM_1ug_26.raw	Raw
	20210322_ProAlanase_0-5mM_1ug_28.raw	Raw
	20210322_ProAlanase_0-5mM_1ug_30.raw	Raw
	20210322_ProAlanase_0mM_1ug_19.raw	Raw
	20210322_ProAlanase_0mM_1ug_21.raw	Raw

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Publications

Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes.

Donnellan Leigh L Young Clifford C Simpson Bradley S BS Dhillon Varinderpal S VS Costabile Maurizio M Hoffmann Peter P Fenech Michael M Deo Permal P

International journal of molecular sciences 20220408 8

The accurate segregation of sister chromatids is complex, and errors that arise throughout this process can drive chromosomal instability and tumorigenesis. We recently showed that methylglyoxal (MGO), a glycolytic by-product, can cause chromosome missegregation events in lymphocytes. However, the underlying mechanisms of this were not explored. Therefore, in this study, we utilised shotgun proteomics to identify MGO-modified proteins, and label-free quantitation to measure changes in protein ab ...[more]

PMID: 35456956

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