Reactions of cysteine, its derivatives, glutathione, coenzyme A, and dihydrolipoic acid with isothiocyanates

Podhradský, Dušan; Drobnica, L; Kristián, Pavol

doi:10.1007/bf01920581

Cited by 58 publications

(58 citation statements)

References 11 publications

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“…The electrophilic properties of ITCs enable them to react with cellular sulfhydryl groups, including cysteines in proteins, leading to a modification of the protein structure or activity. ITC can also react with amine groups but with a lesser affinity (76). Not all cysteines are capable of reacting with ITCs: hydrophobicity and steric hindrance influence the reactivity of cysteines toward electrophilic compounds (74,77).…”

Section: Discussionmentioning

confidence: 99%

Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

Dufour

Ståhl

Rosenfeld

et al. 2013

Appl Environ Microbiol

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cCampylobacter jejuni is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anticancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood. We investigated the early cellular response of C. jejuni to benzyl isothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of C. jejuni to benzyl isothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. Oxygen consumption was progressively impaired by benzyl isothiocyanate treatment, as revealed by high-resolution respirometry, while the ATP content increased soon after benzyl isothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzyl isothiocyanate induced intracellular protein aggregation. These results indicate that benzyl isothiocyanate affects C. jejuni by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death.

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Section: Discussionmentioning

confidence: 99%

Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

Dufour

Ståhl

Rosenfeld

et al. 2013

Appl Environ Microbiol

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“…1). ITCs react with a-amino groups in N-terminal residues and/or amino groups of lysine through alkylation at a rate at least 1000 times less than that of thiocarbamation (Podhradský et al, 1979). Cysteine, when highly conserved in proteins, plays a crucial role in protein structure and regulatory function owing to the ability of thiol groups to stabilize protein structure with covalent disulfide bonds, to coordinate metal ions, and to confer redox properties.…”

Section: Chemistry Of Itcsmentioning

confidence: 99%

“…ITC-thiol adducts are spontaneously generated but their formation is also catalysed by specialized enzymes (glutathione S-transferases, GST) when the target is the small thiol glutathione (GSH, c-Lglutamyl-L-cysteinyl-L-glycine). The reactivity of specific amines and thiols in target proteins also depends on their pK a values, which are affected by surrounding amino acid residues (Podhradský et al, 1979;Snyder et al, 1981). Not all cysteine residues are reactive toward electrophiles.…”

Section: Plant Tissue Gutmentioning

confidence: 99%

The antibacterial properties of isothiocyanates

2015

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Isothiocyanates (ITCs) are natural plant products generated by the enzymic hydrolysis of glucosinolates found in Brassicaceae vegetables. These natural sulfur compounds and their dithiocarbamate conjugates have been previously evaluated for their anti-cancerous properties. Their antimicrobial properties have been previously studied as well, mainly for food preservation and plant pathogen control. Recently, several revelations concerning the mode of action of ITCs in prokaryotes have emerged. This review addresses these new studies and proposes a model to summarize the current knowledge and hypotheses for the antibacterial effect of ITCs and whether they may provide the basis for the design of novel antibiotics.

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“…Because FITC labels the deprotonated SH group and amino group (24), it was necessary to determine whether inhibition of P i uptake via the phosphate carrier by FITC was due to the labeling of cysteine and/or lysine residues in the carrier. We examined the effect of DTT on P i uptake by mitochondria labeled with FITC.…”

Section: Effect Of Fitc On Mitochondrialmentioning

confidence: 99%

Specific Labeling of the Bovine Heart Mitochondrial Phosphate Carrier with Fluorescein 5-Isothiocyanate

Majima

Ishida

Miki

et al. 2001

Journal of Biological Chemistry

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The amine/SH-modifying fluorescein 5-isothiocyanate (FITC) specifically labeled Lys 185 in the putative membrane-spanning region of the phosphate carrier from both the cytosolic and matrix sides of bovine heart mitochondria at 0°C and pH 7.2, and the labeling inhibited the phosphate transport. Nonmodifying fluorescein derivatives having similar structural features to those of ADP and ATP (Majima, E., Yamaguchi, N., Chuman, H., Shinohara, Y., Ishida, M., Goto, S., and Terada, H. (1998) Biochemistry 37, 424 -432) inhibited the specific FITC labeling and phosphate transport, but the nonfluorescein phenylisothiocyanate did not inhibit FITC labeling, suggesting that there is a region recognizing the adenine nucleotides in the phosphate carrier and that this region is closely associated with the transport activity. The phosphate transport inhibitor pyridoxal 5-phosphate inhibited the specific FITC labeling, possibly due to competitive modification of Lys 185 . In addition, FITC inhibited the ADP transport and specific labeling of the ADP/ATP carrier with the fluorescein SH reagent eosin 5-maleimide. Based on these results, we discuss the structural features of the phosphate carrier in relation to its transport activity.There are various solute carriers in the mitochondrial inner membrane to support ATP synthesis by oxidative phosphorylation. The 30-kDa solute carriers, consisting of a three-repeat structure containing a certain consensus sequence, are members of the mitochondrial solute carrier family (1). Of these, the ADP/ATP carrier mediating transport of ADP and ATP, the phosphate carrier mediating the symport of orthophosphate (P i ) and H ϩ , and the type 1 uncoupling protein forming the short circuit of the proton current (2-4) have received considerable attention. These carriers take similar topologies of six transmembrane helices with three large hydrophilic loops facing the matrix, and their homodimers are thought to be their functional units (2,3,5,6). However, their precise structural characteristics are not fully understood in relation to their transport functions.Because fluorescein derivatives have been thought to have similar structural features to those of adenine nucleotides (7, 8), they have been used as fluorescent probes in studies on the kinetics and conformational changes caused by their interactions with the adenine nucleotide binding sites of proteins such as ATPases (9 -11), NAD(P) ϩ -dependent dehydrogenases (12, 13), and kinases (7,8). In fact, we recently reported that the geometric and electronic structures of fluorescein analogs are very similar to those of ADP/ATP (14). In addition, we found that various fluorescein derivatives have high affinities to the ADP/ATP carrier in bovine heart mitochondria, and the binding leads to inhibition of the transport activity (4,14,15). Of the fluorescein analogs, the SH reagent eosin 5-maleimide (EMA) 1 most significantly interacts with the ADP/ATP carrier; it quickly and specifically labels Cys 159 in the second loop facing the matrix of the bovine ...

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Reactions of cysteine, its derivatives, glutathione, coenzyme A, and dihydrolipoic acid with isothiocyanates

Cited by 58 publications

References 11 publications

Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

The antibacterial properties of isothiocyanates

Specific Labeling of the Bovine Heart Mitochondrial Phosphate Carrier with Fluorescein 5-Isothiocyanate

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