Chemoproteomics Reveals Chemical Diversity and Dynamics of 4-Oxo-2-nonenal Modifications in Cells

Sun, Rui; Fu, Ling; Liu, Keke; Tian, Caiping; Yang, Yong; Tallman, Keri A.; Porter, Ned A.; Liebler, D.C.; Yang, Jing

doi:10.1074/mcp.ra117.000116

Cited by 27 publications

(39 citation statements)

References 67 publications

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“…Among them, a benzothiazine‐based probe, called BTD, exhibits the highest level of S‐sulfenylome reactivity ( k obs =1700 M −1 sec −1 ), which represents a rate enhancement of more than two orders of magnitude compared to the dimedone‐based probe, DYn‐2 ( k obs =10 M −1 sec −1 ) (Gupta et al., ). BTD demonstrated to be highly compatible with the site‐centric chemoproteomic platform (Fu et al., ; Sun et al., , ; Tian et al., ; Yang et al., ). Therefore, the new BTD probe can be used to globally, site‐specifically map and quantify cysteine S‐sulfenylation in complex proteomes in a much more efficient manner.…”

Section: Commentarymentioning

confidence: 99%

Proteome‐Wide Analysis of Cysteine S‐Sulfenylation Using a Benzothiazine‐Based Probe

Liu

Ferreira

et al. 2018

CP Protein Science

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Oxidation of a protein cysteinyl thiol (Cys‐SH) to S‐sulfenic acid (Cys‐SOH) by a reactive oxygen species (e.g., hydrogen peroxide), which is termed protein S‐sulfenylation, is a reversible post‐translational modification that plays a crucial role in redox regulation of protein function in various biological processes. Due to its intrinsically labile nature, protein S‐sulfenylation cannot be directly detected or analyzed. Chemoselective probing has been the method of choice for analyzing S‐sulfenylated proteins either in vitro or in situ, as it allows stabilization and direct detection of this transient oxidative intermediate. However, it remains challenging to globally pinpoint the specific S‐sulfenylated cysteine sites on complex proteomes and to quantify their dynamic changes upon oxidative stress. This unit describes how a benzothiazine‐based chemoselective probe called BTD and mass spectrometry based chemoproteomics can be used to globally and site‐specifically identify and quantify protein S‐sulfenylation. © 2018 by John Wiley & Sons, Inc.

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Section: Commentarymentioning

confidence: 99%

Proteome‐Wide Analysis of Cysteine S‐Sulfenylation Using a Benzothiazine‐Based Probe

Liu

Ferreira

et al. 2018

CP Protein Science

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“…The stability of adducts formed will be influenced by several factors including the nature of the adducted residue and the occurrence of additional intramolecular reactions [ 58 ]. Moreover, both, non-enzymatic and enzymatic reversal of certain electrophilic lipid-protein adducts has been reported in vitro as well as in cellular models [ [59] , [60] , [61] ]. Therefore, lipoxidation can constitute a dynamic modification contributing to signaling mechanisms [ 60 , 61 ].…”

Section: Introductionmentioning

confidence: 99%

Type III intermediate filaments as targets and effectors of electrophiles and oxidants

Viedma-Poyatos

Pajares

2020

Redox Biology

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Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications, elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target.

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“…MS 1 precursor quantitation was performed as described previously (26,27). The retention time of the identified peptide was used to position a retention time window (± 2.0 min) across the run lacking the same peptide identification.…”

Section: Humanmentioning

confidence: 99%

Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug-Metabolizing Enzymes as a Response to Redox Alteration

Albertolle

Phan

Pozzi

et al. 2018

Molecular & Cellular Proteomics

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2The abbreviations used are: CID, collision-induced dissociation; DTT, dithiothreitol; ER, endoplasmic reticulum; FDR, (peptide) false discovery rate; FMO, microsomal flavin-containing monooxygenase; HCD, higher energy collisional dissociation; HEPPS, 3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonate; ICDID, isotope-coded dimedone/iododimedone (labeling); MAO, monoamine oxidase; P450 or CYP, cytochrome P450; TCEP, tris(carbethoxymethyl)phosphine;UGT, UDP-glucuronyl transferase. SUMMARYThe lumen of the endoplasmic reticulum (ER) provides an oxidizing environment to aid in the formation of disulfide bonds, which is tightly regulated by both antioxidant proteins and small molecules. On the cytoplasmic side of the ER, cytochrome P450 (P450) proteins have been identified as a superfamily of enzymes that are important in the formation of endogenous chemicals as well as in the detoxication of xenobiotics. Our previous report described oxidative inhibition of P450 Family 4 enzymes via oxidation of the heme-thiolate cysteine to a sulfenic acid (-SOH) (Albertolle, M. E. et al. (2017) J. Biol. Chem. 292, 11230-11242). Further proteomic analyses of murine kidney and liver microsomes led to the finding that a number of other drug metabolizing enzymes located in the ER are also redox-regulated in this manner. We expanded our analysis of sulfenylated enzymes to human liver and kidney microsomes. Evaluation of the sulfenylation, catalytic activity, and spectral properties of P450s 1A2, 2C8, 2D6, and 3A4 led to the identification of two classes of redox sensitivity in P450 enzymes: heme thiolate-sensitive and thiol-insensitive. These findings provide evidence for a mammalian P450 regulatory mechanism, which may also be relevant to other drug-metabolizing enzymes. (Data are available via ProteomeXchange with identifier PXD007913.) (INTRODUCTION)The endoplasmic reticulum (ER) is a site of protein translation, posttranslational processing, and small molecule metabolism (1). Posttranslational processing includes glycosylation of proteins for sorting, disulfide bond formation, and specific proteolytic cleavages.The ER lumen is an oxidizing environment that aids in the production of disulfide bonds, which is maintained at a homeostatic level by both small molecules (ascorbate) and proteins (protein disulfide isomerases) (2, 3). The cytosolic side of the ER remains a reducing environment to preserve the normal function of integral ER proteins.Cytochromes P450 (CYP, P450) are found in the cytoplasmic side of the ER and are most well-known for the ability to metabolize xenobiotics and important endogenous substrates (e.g., steroids and vitamins) (4). These proteins have been of interest in the pharmaceutical industry since their initial discovery, and enzymes in P450 Subfamilies 1A, 2C, 2D, and 3A are involved in the metabolism and clearance of a large majority of small molecule drugs currently approved for clinical use in humans (4). P450 regulation involves genetic and epigenetic aspects, as well as transcriptional regulation by bot...

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Chemoproteomics Reveals Chemical Diversity and Dynamics of 4-Oxo-2-nonenal Modifications in Cells

Cited by 27 publications

References 67 publications

Proteome‐Wide Analysis of Cysteine S‐Sulfenylation Using a Benzothiazine‐Based Probe

Proteome‐Wide Analysis of Cysteine S‐Sulfenylation Using a Benzothiazine‐Based Probe

Type III intermediate filaments as targets and effectors of electrophiles and oxidants

Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug-Metabolizing Enzymes as a Response to Redox Alteration

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