PLP-dependent H2S biogenesis

Singh, Siddharth; Banerjee, Ruma

doi:10.1016/j.bbapap.2011.02.004

Cited by 172 publications

(170 citation statements)

References 99 publications

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“…In addition, homocysteine and cysteine were reported to be substrates for H 2 S production by the trans-sulfuration enzymes in mammals (39). Therefore, a possible mechanism of toxicity could be the conversion of SeHCys and/or SeCys to H 2 Se by cystathionine ␥-lyase (Cys3p).…”

Section: H 2 Se Production Is Not Involved In Semetmentioning

confidence: 99%

Trans-sulfuration Pathway Seleno-amino Acids Are Mediators of Selenomethionine Toxicity in Saccharomyces cerevisiae*

Lazard

Dauplais

Blanquet

et al. 2015

Journal of Biological Chemistry

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Background:The mechanisms underlying selenomethionine toxicity are poorly understood. Results: Saccharomyces cerevisiae mutations affecting sulfur metabolism or superoxide degradation impact selenomethionine toxicity. Conclusion: Selenomethionine primarily exerts its toxicity via the seleno-amino acids selenohomocysteine and selenocysteine. Significance: This study highlights the as yet underestimated importance of the trans-sulfuration pathway in selenomethionine toxicity.

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Section: H 2 Se Production Is Not Involved In Semetmentioning

confidence: 99%

Trans-sulfuration Pathway Seleno-amino Acids Are Mediators of Selenomethionine Toxicity in Saccharomyces cerevisiae*

Lazard

Dauplais

Blanquet

et al. 2015

Journal of Biological Chemistry

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“…Maintaining healthy levels of H 2 S in mammalian cells requires tight control of its biosynthesis and its catabolism (8,9). H 2 S is produced endogenously by two enzymes in the transsulfuration pathway, cystathionine β-synthase and γ-cystathionase as well as by mercaptopyruvate sulfurtransferase (MST) (10)(11)(12)(13). H 2 S is oxidized via the sulfide oxidation pathway to generate the end-products thiosulfate and sulfate via the concerted action of the mitochondrial enzymes sulfide quinone oxidoreductase, persulfide dioxygenase, rhodanese and sulfite oxidase (14)(15)(16).…”

Section: Hydrogen Sulfide (H 2 S)mentioning

confidence: 99%

Thiosulfate sulfurtransferase-like domain–containing 1 protein interacts with thioredoxin

Libiad

Motl

Akey

et al. 2018

Journal of Biological Chemistry

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ǂ These authors contributed equally to this work Rhodanese domains are structural modules present in the sulfurtransferase superfamily. These domains can exist as single units, in tandem repeats or fused to domains with other activities. Despite their prevalence across species, the specific physiological roles of most sulfurtransferases are not known. Mammalian rhodanese and mercaptopyruvate sulfurtransferase are perhaps the best-studied members of this protein superfamily and are involved in hydrogen sulfide metabolism. The relatively unstudied human thiosulfate sulfurtransferase like domain-containing 1 (TSTD1) protein, a single-domain cytoplasmic sulfurtransferase, was also postulated to play a role in the sulfide oxidation pathway using thiosulfate to form glutathione persulfide, for subsequent processing in the mitochondrial matrix. Prior kinetic analysis of TSTD1 was performed at pH 9.2, raising questions about relevance and the proposed model for TSTD1 function. In this study, we report a 1.04 Å resolution crystal structure of human TSTD1, which displays an exposed active site that is distinct from that of rhodanese and mercaptopyruvate sulfurtransferase. Kinetic studies with a combination of sulfur donors and acceptors reveal that TSTD1 exhibits a low K M for thioredoxin as a sulfane sulfur acceptor and that it utilizes thiosulfate inefficiently as a sulfur donor. The active site exposure and its interaction with thioredoxin, suggest that TSTD1 might play a role in sulfide-based signaling. The apical localization of TSTD1 in human colonic crypts, which interfaces with sulfide-releasing microbes, and the overexpression of TSTD1 in colon cancer, provides potentially intriguing clues as to its role in sulfide metabolism. Hydrogen sulfide (H 2 S)1 is an important signaling molecule with effects on multiple physiological processes including neuromodulation, inflammation and cardiac function (1-7). Maintaining healthy levels of H 2 S in mammalian cells requires tight control of its biosynthesis and its catabolism (8,9). H 2 S is produced endogenously by two enzymes in the transsulfuration pathway, cystathionine β-synthase and γ-cystathionase as well as by mercaptopyruvate sulfurtransferase (MST) (10-13). H 2 S is oxidized via the sulfide oxidation pathway to generate the end-products thiosulfate Protein persulfidation, a posttranslational modification of cysteine residues, is postulated to be a major mechanism by which H 2 S signals (17). However, the mechanism by which target proteins acquire this modification and the sulfur source(s) used in persulfidation reactions are unclear (18). Sulfurtransferases like rhodanese or the single rhodanese domain containing TSTD1 could potentially play a role in protein persulfidation because of their capacity to form an active site cysteine persulfide during their reaction cycle (18).The rhodanese superfamily members are distinguished by a structural module with an α/β topology in which α-helices surround a central five-stranded β-sheet core (19). At least three variations...

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“…2D). The catalysis involves two separate pockets of CBS, one, where the PLP external aldimine is formed and a separate one, where the nucleophilic amino acid is bound (107,108).…”

Section: Enzymology Expression and Transcriptional Regulation Of Cbsmentioning

confidence: 99%

“…For detailed information on the enzymology, tissue expression levels, and transcriptional and post-transcriptional regulation of CBS, we refer the reader to multiple specialized reviews (7,51,76,77,107). CBS (EC 4.2.1.22) is traditionally introduced as the first enzyme of the transsulfuration pathway.…”

Section: Enzymology Expression and Transcriptional Regulation Of Cbsmentioning

confidence: 99%

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

Hellmich

Coletta

Chao

et al. 2015

Antioxidants & Redox Signaling

203

186

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Significance: Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways. Recent Advances: In colorectal and ovarian cancers, an increase in the intratumor production of hydrogen sulfide (H 2 S) from cystathionine b-synthase (CBS) plays an important role in promoting the cellular bioenergetics, proliferation, and migration of cancer cells. It also stimulates peritumor angiogenesis inhibition or genetic silencing of CBS exerts antitumor effects both in vitro and in vivo, and potentiates the antitumor efficacy of anticancer therapeutics. Critical Issues: Recently published studies are reviewed, implicating CBS overexpression and H 2 S overproduction in tumor cells as a tumorgrowth promoting ''bioenergetic fuel'' and ''survival factor,'' followed by an overview of the experimental evidence demonstrating the anticancer effect of CBS inhibition. Next, the current state of the art of pharmacological CBS inhibitors is reviewed, with special reference to the complex pharmacological actions of aminooxyacetic acid. Finally, new experimental evidence is presented to reconcile a controversy in the literature regarding the effects of H 2 S donor on cancer cell proliferation and survival. Future Directions: From a basic science standpoint, future directions in the field include the delineation of the molecular mechanism of CBS upregulation of cancer cells and the delineation of the interactions of H 2 S with other intracellular pathways of cancer cell metabolism and proliferation. From the translational science standpoint, future directions include the translation of the recently emerging roles of H 2 S in cancer into human diagnostic and therapeutic approaches. Antioxid. Redox Signal. 22,

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PLP-dependent H2S biogenesis

Cited by 172 publications

References 99 publications

Trans-sulfuration Pathway Seleno-amino Acids Are Mediators of Selenomethionine Toxicity in Saccharomyces cerevisiae*

Trans-sulfuration Pathway Seleno-amino Acids Are Mediators of Selenomethionine Toxicity in Saccharomyces cerevisiae*

Thiosulfate sulfurtransferase-like domain–containing 1 protein interacts with thioredoxin

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

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