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Toru Komatsu - One of the best experts on this subject based on the ideXlab platform.
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discovery and mechanistic characterization of selective inhibitors of h2s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or −1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
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discovery and mechanistic characterization of selective inhibitors of h 2 s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or -1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
Kenjiro Hanaoka - One of the best experts on this subject based on the ideXlab platform.
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discovery and mechanistic characterization of selective inhibitors of h2s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or −1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
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discovery and mechanistic characterization of selective inhibitors of h 2 s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or -1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
Josef Hormes - One of the best experts on this subject based on the ideXlab platform.
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Utilization of 'elemental' Sulfur by different phototrophic Sulfur bacteria (Chromatiaceae, Ectothiorhodospiraceae): A Sulfur K-edge XANES spectroscopy study
Journal of Physics: Conference Series, 2009Co-Authors: Bettina Franz, Henning Lichtenberg, Christiane Dahl, Josef Hormes, Alexander PrangeAbstract:Phototrophic Sulfur bacteria are generally able to use elemental Sulfur as an electron donor for anoxygenic photosynthesis. Elemental Sulfur is mainly a mixture of cyclo-octaSulfur and polymeric Sulfur. The purple Sulfur bacterium Allochromatium vinosum strongly prefers the polymeric Sulfur fraction showing that Sulfur speciation has a strong influence on availability of elemental Sulfur. X-ray absorption near edge structure (XANES) spectroscopy was used to investigate whether polymeric Sulfur is also the preferred Sulfur species in other purple Sulfur bacteria belonging to the families Chromatiaceae and Ecothiorodospiraceae. The cultures were fed with 50 mM of elemental Sulfur consisting of 68% polymeric Sulfur and 30% cyclo-octaSulfur. In all cultures, elemental Sulfur was converted into intra- or extracellular Sulfur globules, respectively, and further oxidized to sulfate. Sulfate concentrations were determined by HPLC and turbidometric assays, respectively. However, the added elemental Sulfur was only partly used by the bacteria, one part of the 'elemental Sulfur' remained in the cultures and was not taken up. XANES spectroscopy revealed that only the polymeric Sulfur fraction was taken up by all cultures investigated. This strongly indicates that polymeric 'chain-like' Sulfur is the form preferably used by phototrophic Sulfur bacteria.
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utilization of solid elemental Sulfur by the phototrophic purple Sulfur bacterium allochromatium vinosum a Sulfur k edge x ray absorption spectroscopy study
Microbiology, 2007Co-Authors: Bettina Franz, Henning Lichtenberg, Christiane Dahl, Josef Hormes, Hartwig Modrow, Alexander PrangeAbstract:The purple Sulfur bacterium Allochromatium vinosum can use elemental Sulfur as an electron donor for anoxygenic photosynthesis. The elemental Sulfur is taken up, transformed into intracellular Sulfur globules and oxidized to sulfate. Commercially available "elemental" Sulfur usually consists of the two species cyclo-octaSulfur and polymeric Sulfur. The authors investigated whether only one Sulfur species is used or at least preferred when Alc. vinosum takes up elemental Sulfur and forms globules. To this end, Alc. vinosum was cultivated photolithoautotrophically with two types of elemental Sulfur that differed in their cyclo-octaSulfur : polymeric Sulfur ratio, as well as with pure polymeric Sulfur. Sulfur speciation was analysed using X-ray absorption spectroscopy, and sulfate contents were determined by HPLC to quantify the amount of elemental Sulfur being taken up and oxidized by Alc. vinosum. The results show that Alc. vinosum uses only the polymeric Sulfur (Sulfur chain) fraction of elemental Sulfur and is probably unable to take up and form Sulfur globules from cyclo-octaSulfur. Furthermore, direct cell-Sulfur contact appears to be necessary for uptake of elemental Sulfur by Alc. vinosum.
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speciation of Sulfur from filamentous microbial mats from sulfidic cave springs using x ray absorption near edge spectroscopy
Fems Microbiology Letters, 2007Co-Authors: Annette Summers Engel, Henning Lichtenberg, Josef Hormes, Alexander PrangeAbstract:Most transformations within the Sulfur cycle are controlled by the biosphere, and deciphering the abiotic and biotic nature and turnover of Sulfur is critical to understand the geochemical and ecological changes that have occurred throughout the Earth's history. Here, synchrotron radiation-based Sulfur K-edge X-ray absorption near-edge structure (XANES) spectroscopy is used to examine Sulfur speciation in natural microbial mats from two aphotic (cave) settings. Habitat geochemistry, microbial community compositions, and Sulfur isotope systematics were also evaluated. Microorganisms associated with Sulfur metabolism dominated the mats, including members of the Epsilonproteobacteria and Gammaproteobacteria. These groups have not been examined previously by Sulfur K-edge XANES. All of the mats consisted of elemental Sulfur, with greater contributions of cyclo-octaSulfur (S8) compared with polymeric Sulfur (Smicro). While this could be a biological fingerprint for some bacteria, the signature may also indicate preferential oxidation of Smicro and S8 accumulation. Higher sulfate content correlated to less S8 in the presence of Epsilonproteobacteria. Sulfur isotope compositions confirmed that Sulfur content and Sulfur speciation may not correlate to microbial metabolic processes in natural samples, thereby complicating the interpretation of modern and ancient Sulfur records.
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Quantitative speciation of Sulfur in bacterial Sulfur globules: X-ray absorption spectroscopy reveals at least three different species of Sulfur.
Microbiology, 2002Co-Authors: Alexander Prange, Josef Hormes, Hartwig Modrow, Reinhold Chauvistré, Hans G. Trüper, Christiane DahlAbstract:X-ray absorption near edge structure (XANES) spectroscopy at the Sulfur K-edge was applied to probe the speciation of Sulfur of metabolically different Sulfur-accumulating bacteria in situ. Fitting the spectra using a least-square fitting routine XANES reveals at least three different forms of Sulfur in bacterial Sulfur globules. CyclooctaSulfur dominates in the Sulfur globules of Beggiatoa alba and the very recently described giant bacterium Thiomargarita namibiensis. A second type of Sulfur globules is present in Acidithiobacillus ferrooxidans: here the Sulfur occurs as polythionates. In contrast, in purple and green Sulfur bacteria the Sulfur mainly consists of Sulfur chains, irrespective of whether it is accumulated in globules inside or outside the cells. These results indicate that the speciation of Sulfur in the Sulfur globules reflects the different ecological and physiological properties of different metabolic groups of bacteria.
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In situ analysis of Sulfur in the Sulfur globules of phototrophic Sulfur bacteria by X-ray absorption near edge spectroscopy.
Biochimica et Biophysica Acta, 1999Co-Authors: Alexander Prange, Christiane Dahl, Hartwig Modrow, Hans G. Trüper, Isolde Arzberger, Claudia Engemann, Oliver Schumann, Ralf Steudel, Josef HormesAbstract:During the oxidation of sulfide and thiosulfate purple and green Sulfur bacteria accumulate globules of 'elemental' Sulfur. Although essential for a thorough understanding of Sulfur metabolism in these organisms, the exact chemical nature of the stored Sulfur is still unclear. We applied Sulfur K-edge X-ray absorption near edge spectroscopy (XANES) to probe the forms of Sulfur in intact cells. Comparing XANES spectra of Allochromatium vinosum, Thiocapsa roseopersicina, Marichromatium purpuratum, Halorhodospira halophila and Chlorobium vibrioforme grown photolithoautotrophically on sulfide with reference probes (fingerprint method), we found Sulfur chains with the structure R-S(n)-R. Evidence for the presence of Sulfur rings, polythionates and anionic polysulfides in the Sulfur globules of these bacteria was not obtained.
Norihiro Shibuya - One of the best experts on this subject based on the ideXlab platform.
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discovery and mechanistic characterization of selective inhibitors of h2s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or −1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
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discovery and mechanistic characterization of selective inhibitors of h 2 s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or -1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
Takuya Terai - One of the best experts on this subject based on the ideXlab platform.
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discovery and mechanistic characterization of selective inhibitors of h2s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or −1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
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discovery and mechanistic characterization of selective inhibitors of h 2 s producing enzyme 3 mercaptopyruvate Sulfurtransferase 3mst targeting active site cysteine persulfide
Scientific Reports, 2017Co-Authors: Kenjiro Hanaoka, Norihiro Shibuya, Yusuke Suwanai, Kazuhito Shimamoto, Kiyoshi Sasakura, Sachiko Tomafukai, Yoko Takano, Takuya Terai, Toru KomatsuAbstract:Very recent studies indicate that Sulfur atoms with oxidation state 0 or -1, called sulfane Sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate Sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane Sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane Sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a perSulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the perSulfur anion of the perSulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.
