1.14.99.50: gamma-glutamyl hercynylcysteine S-oxide synthase
This is an abbreviated version!
For detailed information about gamma-glutamyl hercynylcysteine S-oxide synthase, go to the full flat file.
Word Map on EC 1.14.99.50
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1.14.99.50
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egtbs
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ergothioneine
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ovoas
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ovothiols
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sulfur
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mycobacterium
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synthases
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nonheme
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proteobacteria
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carbon-sulfur
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chloracidobacterium
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iron-dependent
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dioxygenase
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thermophilum
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thermoresistibile
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sulfur-containing
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diatom
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thiolate
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o2-dependent
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synthesis
- 1.14.99.50
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egtbs
- ergothioneine
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ovoas
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ovothiols
- sulfur
- mycobacterium
- synthases
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nonheme
- proteobacteria
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carbon-sulfur
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chloracidobacterium
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iron-dependent
- dioxygenase
- thermophilum
- thermoresistibile
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sulfur-containing
- diatom
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thiolate
-
o2-dependent
- synthesis
Reaction
Synonyms
5-histidylcysteine sulfoxide synthase, Cabther_A1318, EgtB, EgtBthermo, hercynine oxygenase, sulfoxide synthase
ECTree
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General Information
General Information on EC 1.14.99.50 - gamma-glutamyl hercynylcysteine S-oxide synthase
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evolution
malfunction
a single point mutation Y377F converts this enzyme into a gamma-glutamyl cysteine dioxygenase with an efficiency that rivals naturally evolved thiol dioxygenases
metabolism
physiological function
additional information
enzyme EgtB represents a distinct enzyme class (sulfoxide synthases) with no relation to sulfur oxidizing or C-S bond-forming iron enzymes such as cysteine dioxygenase or isopenicillin synthase
evolution
the two known sulfoxide synthases EgtB and OvoA distinguish themselves from each other by their substrate preferences and product C-S bond regioselectivity
evolution
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EgtB contains a strongly conserved HX3HXE motif, implying that it is a member of the facial triad enzyme family with the Fe(II) site ligated by 2-His-1-Glu
evolution
enzyme EgtB belongs to the mononuclear nonheme iron dioxygenase family
evolution
OvoA, EC 1.14.99.52, and EgtB are related in sequence, while they are biochemically distinct
evolution
Some cyanobacteria recruited and adapted a sulfoxide synthase from a different biosynthetic pathway to make ergothioneine. Evolutionary malleability of the thiohistidine biosynthetic machinery. The sulfoxide synthase EgtB catalyzes the sulfurization of N-alpha-trimethylhistidine at the imidazole 2-position and subsequent oxidation to the S-sulfoxide. The homologous sulfoxide synthases OvoA, EC 1.14.99.52, catalyze the formation of 5-histidylcysteine sulfoxide. The stereochemistry of this sulfoxide is unknown, and cyanobacterial OvoA homologues (Egt-B(ovo)) have evolved to catalyze an EgtB-type reaction by convergent evolution. Prokaryotic EgtBs are usually monofunctional, fungal EgtBs are fused to EgtD
evolution
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enzyme EgtB belongs to the mononuclear nonheme iron dioxygenase family
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evolution
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OvoA, EC 1.14.99.52, and EgtB are related in sequence, while they are biochemically distinct
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evolution
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the two known sulfoxide synthases EgtB and OvoA distinguish themselves from each other by their substrate preferences and product C-S bond regioselectivity
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the enzyme is part of the biosynthesis pathway of ergothioneine
metabolism
the enzyme is part of the biosynthesis pathway of ergothioneine
metabolism
enzyme EgtB catalyzes O2-dependent C-S bond formation between gamma-glutamyl cysteine and N-alpha-trimethyl histidine as the central step in ergothioneine biosynthesis
metabolism
the enzyme catalyzes a step in the ergothioneine biosynthetic pathway, overview
metabolism
the enzyme is involved in the ergothioneine biosynthesis catalyzing a direct four-electron oxidative process, coupling between hercynine and gamma-L-glutamyl-L-cysteine, overview
metabolism
biosynthesis of N-alpha-trimethyl-2-thiohistidine (ergothioneine) is a frequent trait in cyanobacteria. This sulfur compound may provide essential relief from oxidative stress related to oxygenic photosynthesis. The central steps in ergothioneine biosynthesis are catalyzed by a histidine methyltransferase and the iron-dependent sulfoxide synthase. Ergothioneine biosynthesis starts by trimethylation of the alpha-amino group of histidine. The resulting N-alpha-trimethylhistidine (TMH) is fused to either gamma-glutamylcysteine (in actinomycetes, EC 1.14.99.50) or cysteine (in fungi, EC 1.14.99.51). The sulfoxide product is converted into ergothoneine by removal of the glutamyl and cysteinyl moieties
metabolism
EgtB is a nonheme iron enzyme catalyzing the C-S bond formation between gamma-glutamyl cysteine and N-alpha-trimethyl histidine in the ergothioneine biosynthesis
metabolism
the enzyme catalyzes the key step in the biosynthesis of ergothioneine
metabolism
the mononuclear non-heme iron enzyme EgtB catalyzes an oxidative C-S bond formation in the ergothioneine biosynthesis. One of the EgtB substrates is gamma-Glu-Cys, which is part of the glutathione biosynthesis, resulting in competition between ergothioneine and glutathione biosyntheses
metabolism
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the enzyme catalyzes the key step in the biosynthesis of ergothioneine
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metabolism
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EgtB is a nonheme iron enzyme catalyzing the C-S bond formation between gamma-glutamyl cysteine and N-alpha-trimethyl histidine in the ergothioneine biosynthesis
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metabolism
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the mononuclear non-heme iron enzyme EgtB catalyzes an oxidative C-S bond formation in the ergothioneine biosynthesis. One of the EgtB substrates is gamma-Glu-Cys, which is part of the glutathione biosynthesis, resulting in competition between ergothioneine and glutathione biosyntheses
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metabolism
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the enzyme catalyzes a step in the ergothioneine biosynthetic pathway, overview
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metabolism
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the enzyme is involved in the ergothioneine biosynthesis catalyzing a direct four-electron oxidative process, coupling between hercynine and gamma-L-glutamyl-L-cysteine, overview
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enzyme EgtB catalyzes O2-dependent C-S bond formation between gamma-glutamyl cysteine and N-alpha-trimethyl histidine as the central step in ergothioneine biosynthesis
physiological function
EgtB from Mycobacterium thermoresistibile catalyzes O2-dependent sulfur-carbon bond formation between the side chains of Nalpha-trimethyl histidine and gamma-glutamyl cysteine as a central step in ergothioneine biosynthesis
physiological function
sulfoxide synthase EgtB represents is a non-heme iron enzyme that catalyzes the formation of a C-S bond between N-alpha-trimethyl histidine and gamma-glutamyl cysteine, which is the key step in the biosynthesis of ergothioneine, an important amino acid related to aging
physiological function
EgtB of Candidatus Chloracidobacterium thermophilum has both EgtB- and Egt1-type of activities, i.e. reactions of EC 1.14.99.50 and EC 1.21.3.10
physiological function
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sulfoxide synthase EgtB represents is a non-heme iron enzyme that catalyzes the formation of a C-S bond between N-alpha-trimethyl histidine and gamma-glutamyl cysteine, which is the key step in the biosynthesis of ergothioneine, an important amino acid related to aging
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the two substrates and three histidine residues serve as ligands in an octahedral iron binding active site, enzyme structure analysis, detailed overview
additional information
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the two substrates and three histidine residues serve as ligands in an octahedral iron binding active site, enzyme structure analysis, detailed overview
additional information
density functional theory modeling of active-site models of EgtB in a polarized continuum model propose a reaction mechanism starting with sulfoxidation (OAT) of gammaGC followed by C-S bond formation and deprotonation (PT) to form products. Optimized QM geometry of the S-O bond formation transition state for the reaction of iron(III)-superoxo with cysteine in EgtB, overview
additional information
in a competitive reaction containing 1 mM of each histidine, N-alpha-trimethylhistidine, and cysteine, OvoAErwin produces only S-(L-histidin-5-yl)-L-cysteine S-oxide, whereas OvoAErw-NW and EgtB(ovo) produce exclusively gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide
additional information
in the active site, the metal is hexacoordinated and ligated by three histidines (His51, His134, and His138), the two substrates (via a sulfide of gamma-glutamyl cysteine and an imidazole nitrogen of N-alpha-trimethyl histidine), and a water molecule. Second-shell residue, Tyr377 forms a hydrogen bond with the water molecule. In addition, two positively charged residues, Arg90 and Arg87, form hydrogen bonds with the substrate gamma-glutamyl cysteine. Several additional water molecules form a hydrogen bonding network interacting with the two substrates
additional information
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density functional theory modeling of active-site models of EgtB in a polarized continuum model propose a reaction mechanism starting with sulfoxidation (OAT) of gammaGC followed by C-S bond formation and deprotonation (PT) to form products. Optimized QM geometry of the S-O bond formation transition state for the reaction of iron(III)-superoxo with cysteine in EgtB, overview
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additional information
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in the active site, the metal is hexacoordinated and ligated by three histidines (His51, His134, and His138), the two substrates (via a sulfide of gamma-glutamyl cysteine and an imidazole nitrogen of N-alpha-trimethyl histidine), and a water molecule. Second-shell residue, Tyr377 forms a hydrogen bond with the water molecule. In addition, two positively charged residues, Arg90 and Arg87, form hydrogen bonds with the substrate gamma-glutamyl cysteine. Several additional water molecules form a hydrogen bonding network interacting with the two substrates
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