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Information on EC 1.14.99.52 - L-cysteinyl-L-histidinylsulfoxide synthase
for references in articles please use BRENDA:EC1.14.99.52
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EC Tree 1 Oxidoreductases
1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
1.14.99 Miscellaneous
1.14.99.52 L-cysteinyl-L-histidinylsulfoxide synthase
IUBMB Comments
Requires Fe2+ for activity. The enzyme participates in ovothiol biosynthesis. It also has some activity as EC 1.13.11.20, cysteine dioxygenase, and can perform the reaction of EC 1.14.99.50, γ-glutamyl hercynylcysteine sulfoxide synthase, albeit with low activity .
The enzyme appears in viruses and cellular organisms
showSynonyms
plovoa, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5-histidylcysteine sulfoxide synthase
OvoA
OvoA-like protein
OvoAe
OvoA_1
OvoA_2
OvoA
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
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L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
the enzyme catalysis follows an thiol-ene type mechanism, it catalyzes C-S bond formation through an OvoA generated L-cysteine thiyl radical that attacks the unsaturated imidazole ring of L-histidine, overview
L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
the catalytic mechanism proceeds via radical intermediate, oxidation of histidine is thermodynamically most favorable for the formation of a HisNdelta(-H). radical via a proton-coupled electron transfer process, only the ferrous peroxysulfur complexes are sufficiently powerful enough oxidants to generate a histidyl-derived radical, not the superoxo-complexes
L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
catalytic mechanism: C-S bond formation is initiated by formation of a histidyl sp2 radical, formation of a histidyl PI-radical, and electrophilic attack of the iron-coordinated cysteine sulfoxide on histidine. The enzyme OvoA oxidizes cysteine to access an iron(IV)-oxo state (a in Figure 2) which then mediates oxidative sulfurization of histidine
L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
catalytic mechanism: C-S bond formation is initiated by formation of a histidyl sp2 radical, formation of a histidyl PI-radical, and electrophilic attack of the iron-coordinated cysteine sulfoxide on histidine. The enzyme OvoA oxidizes cysteine to access an iron(IV)-oxo state which then mediates oxidative sulfurization of histidine
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L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
the enzyme catalysis follows an thiol-ene type mechanism, it catalyzes C-S bond formation through an OvoA generated L-cysteine thiyl radical that attacks the unsaturated imidazole ring of L-histidine, overview
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-
L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
the catalytic mechanism proceeds via radical intermediate, oxidation of histidine is thermodynamically most favorable for the formation of a HisNdelta(-H). radical via a proton-coupled electron transfer process, only the ferrous peroxysulfur complexes are sufficiently powerful enough oxidants to generate a histidyl-derived radical, not the superoxo-complexes
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-
L-histidine + L-cysteine + O2 = S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
catalytic mechanism: C-S bond formation is initiated by formation of a histidyl sp2 radical, formation of a histidyl PI-radical, and electrophilic attack of the iron-coordinated cysteine sulfoxide on histidine. The enzyme OvoA oxidizes cysteine to access an iron(IV)-oxo state (a in Figure 2) which then mediates oxidative sulfurization of histidine
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SYSTEMATIC NAME
IUBMB Comments
L-histidine,L-cysteine:oxygen [S-(L-histidin-5-yl)-L-cysteine S-oxide-forming]
Requires Fe2+ for activity. The enzyme participates in ovothiol biosynthesis. It also has some activity as EC 1.13.11.20, cysteine dioxygenase, and can perform the reaction of EC 1.14.99.50, gamma-glutamyl hercynylcysteine sulfoxide synthase, albeit with low activity [4].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-fluoro-L-histidine + L-cysteine + O2
S-(2-fluoro-L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
4-methylimidazole + L-cysteine + O2
? + H2O
Substrates: very low activity
Products: -
Products: -
?
D-histidine + L-cysteine + O2
S-(D-histidin-5-yl)-L-cysteine S-oxide + S-(D-histidin-2-yl)-L-cysteine S-oxide + H2O
hercynine + gamma-L-glutamyl-L-cysteine + O2
gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
D-histidine + L-cysteine + O2
S-(D-histidin-5-yl)-L-cysteine S-oxide + S-(D-histidin-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: the reaction product as a mixture of 63% 5-D-histidyl-L-cysteine sulfoxide and 37% 2-D-histidyl-L-cysteine sulfoxide
Products: the reaction product as a mixture of 63% 5-D-histidyl-L-cysteine sulfoxide and 37% 2-D-histidyl-L-cysteine sulfoxide
?
D-histidine + L-cysteine + O2
S-(D-histidin-5-yl)-L-cysteine S-oxide + S-(D-histidin-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: the reaction product as a mixture of 63% 5-D-histidyl-L-cysteine sulfoxide and 37% 2-D-histidyl-L-cysteine sulfoxide
Products: the reaction product as a mixture of 63% 5-D-histidyl-L-cysteine sulfoxide and 37% 2-D-histidyl-L-cysteine sulfoxide
?
hercynine + gamma-L-glutamyl-L-cysteine + O2
gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
hercynine + gamma-L-glutamyl-L-cysteine + O2
gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
hercynine + L-cysteine + O2
S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
hercynine + L-cysteine + O2
S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
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Substrates: reaction of EC 1.14.99.51
Products: -
Products: -
?
hercynine + L-cysteine + O2
S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
histamine + L-cysteine + O2
S-(histamin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
histamine + L-cysteine + O2
S-(histamin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-cysteine + O2
cysteine sulfinic acid + H2O
Substrates: oxidation of cysteine to cysteine sulfinic acid in presence of hercynine or L-histidine
Products: -
Products: -
?
L-cysteine + O2
cysteine sulfinic acid + H2O
Substrates: oxidation of cysteine to cysteine sulfinic acid in presence of hercynine or L-histidine
Products: -
Products: -
?
L-cysteine + O2
L-cystine + H2O
Substrates: oxidation of cysteine to cystine
Products: -
Products: -
?
L-cysteine + O2
L-cystine + H2O
Substrates: oxidation of cysteine to cystine
Products: -
Products: -
?
L-histidinamide + L-cysteine + O2
S-(L-histidinamide-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidinamide + L-cysteine + O2
S-(L-histidinamide-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: evaluation of the mechanistic feasibility of the various possible iron-oxygen oxidants in the proton-coupled electron transfer process or the electron transfer process, overview
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
-
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
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Substrates: OvoA modifies the C5 position of the imidazole ring of L-His, site selectivity of the transformation
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
-
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: evaluation of the mechanistic feasibility of the various possible iron-oxygen oxidants in the proton-coupled electron transfer process or the electron transfer process, overview
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
-
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
-
Substrates: -
Products: -
Products: -
?
additional information
?
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Substrates: besides catalyzing the four-electron oxidative coupling between histidine and cysteine, enzyme OvoA can also catalyze a direct oxidative coupling between hercynine and cysteine, which can shorten the ergothioneine biosynthetic pathway by two steps. Enzyme OvoA can also catalyze the reaction of egtB between hercynine and gamma-L-glutamyl-L-cysteine, EC 1.14.99.50
Products: -
Products: -
?
additional information
?
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Substrates: OvoA catalyzes efficient in vitro sulfurization of L-histidine, D-histidine, 2-fluoro-L-histidine and compounds other than amino acids. No activity with 4-bromoimidazole, 4(5)-(hydroxymethyl) imidazole, urocanic acid, N-alpha-acetyl-L-histidine, and carnosine, as well as 3-pyridin-2-ylalanine, 3-pyridin-3-ylalanine, 3-(2-thioxo-2,3-dihydro-1H-imidazol-4-yl)-L-alaninamide, 1-methylimidazole, 2,5-diiodo-L-histidine, 5-fluoro-L-histidine, 5-chloro-L-histidine, 5-bromo-L-histidine, and 5-iodo-L-histidine
Products: -
Products: -
?
additional information
?
-
Substrates: OvoA substrate specificity and substrate binding pocket flexibility, NMR analysis, overview
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme catalyzes the oxidative coupling between histidine and cysteine. It can also catalyze the oxidative coupling between hercynine and cysteine, yet with a different regioselectivity, NMR spectroscopic product analysis, overview. Enzyme OvoA can also catalyze the oxidation of cysteine to either cysteine sulfinic acid or cystine. OvoA-catalyzed reactions can be systematically modulated by a slight modification of one of its substrates, histidine
Products: -
Products: -
?
additional information
?
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Substrates: the ovothiol biosynthetic sulfoxide synthase OvoA from Erwinia tasmaniensis (OvoAErwin) is a promiscuous enzyme. This enzyme is most efficient in making its native product S-(L-histidin-5-yl)-L-cysteine S-oxide, but, when presented with N-alpha-trimethylhistidine as a sulfur acceptor, the enzyme switches product specificity and produces gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide albeit with significantly lower efficiency
Products: -
Products: -
?
additional information
?
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Substrates: when OvoA's native substrate histidine is replaced by hercynine, OvoA can catalyze a one-step transformation reaction of hercynylcysteine S-oxide synthase, EC 1.14.99.51, resulting in kobs changes by 2fold for hercynine, while Km for cysteine increases from 0.3 mM to 3.19 mM. OvoA preferentially uses histidine and cysteine. OvoA also catalyzes the oxidation of cysteine to cysteine sulfinic acid, EC 1.13.11.20. Enzyme activity determination using : a 1H NMR assay of chemical shift of the imidazole hydrogen atoms
Products: -
Products: -
?
additional information
?
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Substrates: OvoA incubated with hercynine (the normal substrate for EgtB, EC 1.14.99.50) and cysteine produces primarily cysteine sulfinic acid, the product of cysteine dioxygenase-type chemistry, cf. EC 1.13.11.20
Products: -
Products: -
?
additional information
?
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Substrates: OvoA catalyzes efficient in vitro sulfurization of L-histidine, D-histidine, 2-fluoro-L-histidine and compounds other than amino acids. No activity with 4-bromoimidazole, 4(5)-(hydroxymethyl) imidazole, urocanic acid, N-alpha-acetyl-L-histidine, and carnosine, as well as 3-pyridin-2-ylalanine, 3-pyridin-3-ylalanine, 3-(2-thioxo-2,3-dihydro-1H-imidazol-4-yl)-L-alaninamide, 1-methylimidazole, 2,5-diiodo-L-histidine, 5-fluoro-L-histidine, 5-chloro-L-histidine, 5-bromo-L-histidine, and 5-iodo-L-histidine
Products: -
Products: -
?
additional information
?
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Substrates: besides catalyzing the four-electron oxidative coupling between histidine and cysteine, enzyme OvoA can also catalyze a direct oxidative coupling between hercynine and cysteine, which can shorten the ergothioneine biosynthetic pathway by two steps. Enzyme OvoA can also catalyze the reaction of egtB between hercynine and gamma-L-glutamyl-L-cysteine, EC 1.14.99.50
Products: -
Products: -
?
additional information
?
-
Substrates: OvoA substrate specificity and substrate binding pocket flexibility, NMR analysis, overview
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme catalyzes the oxidative coupling between histidine and cysteine. It can also catalyze the oxidative coupling between hercynine and cysteine, yet with a different regioselectivity, NMR spectroscopic product analysis, overview. Enzyme OvoA can also catalyze the oxidation of cysteine to either cysteine sulfinic acid or cystine. OvoA-catalyzed reactions can be systematically modulated by a slight modification of one of its substrates, histidine
Products: -
Products: -
?
additional information
?
-
-
Substrates: short cyanobacterial OvoA-type enzymes may contribute to ergothioneine (EC 1.14.99.51) instead of ovothiol production
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
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Substrates: 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
Products: -
Products: -
?
additional information
?
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Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
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Substrates: 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
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
hercynine + gamma-L-glutamyl-L-cysteine + O2
gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
hercynine + gamma-L-glutamyl-L-cysteine + O2
gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
hercynine + gamma-L-glutamyl-L-cysteine + O2
gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
hercynine + L-cysteine + O2
S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
hercynine + L-cysteine + O2
S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
-
Substrates: reaction of EC 1.14.99.51
Products: -
Products: -
?
hercynine + L-cysteine + O2
S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
-
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
Substrates: -
Products: -
Products: -
?
L-histidine + L-cysteine + O2
S-(L-histidin-5-yl)-L-cysteine S-oxide + H2O
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: besides catalyzing the four-electron oxidative coupling between histidine and cysteine, enzyme OvoA can also catalyze a direct oxidative coupling between hercynine and cysteine, which can shorten the ergothioneine biosynthetic pathway by two steps. Enzyme OvoA can also catalyze the reaction of egtB between hercynine and gamma-L-glutamyl-L-cysteine, EC 1.14.99.50
Products: -
Products: -
?
additional information
?
-
-
Substrates: the ovothiol biosynthetic sulfoxide synthase OvoA from Erwinia tasmaniensis (OvoAErwin) is a promiscuous enzyme. This enzyme is most efficient in making its native product S-(L-histidin-5-yl)-L-cysteine S-oxide, but, when presented with N-alpha-trimethylhistidine as a sulfur acceptor, the enzyme switches product specificity and produces gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide albeit with significantly lower efficiency
Products: -
Products: -
?
additional information
?
-
Substrates: besides catalyzing the four-electron oxidative coupling between histidine and cysteine, enzyme OvoA can also catalyze a direct oxidative coupling between hercynine and cysteine, which can shorten the ergothioneine biosynthetic pathway by two steps. Enzyme OvoA can also catalyze the reaction of egtB between hercynine and gamma-L-glutamyl-L-cysteine, EC 1.14.99.50
Products: -
Products: -
?
additional information
?
-
-
Substrates: short cyanobacterial OvoA-type enzymes may contribute to ergothioneine (EC 1.14.99.51) instead of ovothiol production
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
additional information
?
-
Substrates: an OvoA-like protein, full-length OvoA homologue, OvoA_2, is a monofunctional sulfoxide synthase
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Fe2+
a mononuclear non-heme iron enzyme, iron-dependent enzyme, the molecular basis for iron recognition probably maps to a conserved HX3HXE motif in the N-terminal domains of both OvoA
Fe2+
a mononuclear non-heme iron enzyme, dependent on, ligand with 2-His-1-carboxylate facial triad
Fe2+
-
non-heme iron, required for catalysis,residues in the HX3HXE motif might be involved in iron binding
Fe2+
required, the DinB superfamily domain contains the conserved HX3HXE putative iron-binding motif
Fe2+
-
a mononuclear non-heme iron enzyme, iron-dependent enzyme, the molecular basis for iron recognition probably maps to a conserved HX3HXE motif in the N-terminal domains of both OvoA
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
D-isoascorbate
provides a nearly 100fold increase in enzyme activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
free-energy cost calculations for determining the catalytic mechanism, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
collected in the Gulf of Naples, near Castel dell'Ovo, from a location that is not privately-owned or protected in any way, and in collected at the Marine Protected Area Gaiola at station G1 in October of 2013
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
sea urchin Paracentrotus lividus eggs contain high concentrations (in the mM range) of ovothiol A
brenda
sea urchin Strongylocentrotus purpuratus eggs contain high concentrations (in the mM range) of ovothiol C
brenda
PlOvoA embryo expression significantly increased at the pluteus stage
brenda
additional information
enzyme expression analysis, PlOvoA expression profile and response to environmental stress conditions, overview. Ovothiol levels significantly increase at the prism stage after exposure to the metal, with respect to the control, whereas no significant increase is detected at the swimming blastula stage
brenda
additional information
-
enzyme expression analysis, PlOvoA expression profile and response to environmental stress conditions, overview. Ovothiol levels significantly increase at the prism stage after exposure to the metal, with respect to the control, whereas no significant increase is detected at the swimming blastula stage
brenda
additional information
enzyme expression analysis
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
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
enzyme OvoA belongs to the 2-His-1-carboxylate catalytic triad type of mononuclear non-heme iron enzymes
evolution
-
OvoA and EgtB, EC 1.14.99.50, are related in sequence, while they are biochemically distinct
evolution
OvoA evolved in most marine metazoans and was lost in bony vertebrates during the transition from the aquatic to terrestrial environment. The DinB superfamily domain contains the conserved HX3HXE putative iron-binding motif. The residues 581-587, 602-603, 661-663, and 680, considered to be involved in the formation of SAM-binding site, are conserved with the bacterial orthologous gene. OvoA shares two protein domains with EgtB, the DinB superfamily domain and the FGE-sulfatase domain but differs for the additional C-terminal putative SAM-transferase domain. Evolutionary history of OvoA in metazoans, overview
evolution
OvoA evolved in most marine metazoans and was lost in bony vertebrates during the transition from the aquatic to terrestrial environment. Evolutionary history of OvoA in metazoans, overview
evolution
cyanobacterial OvoA homologues (Egt-B(ovo)) have evolved to catalyze an EgtB-type reaction by convergent evolution, cf. EC 1.14.99.50, in a competitive reaction containing 1 mM of each histidine, N-alpha-trimethylhistidine, and cysteine, OvoAErw-NW and EgtB(ovo) produce exclusively gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide
evolution
-
cyanobacterial OvoA homologues (Egt-B(ovo)) have evolved to catalyze an EgtB-type reaction by convergent evolution, cf. EC 1.14.99.50, in a competitive reaction containing 1 mM of each histidine, N-alpha-trimethylhistidine, and cysteine, OvoAErw-NW and EgtB(ovo) produce exclusively gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide
evolution
-
cyanobacterial OvoA homologues (Egt-B(ovo)) have evolved to catalyze an EgtB-type reaction by convergent evolution, cf. EC 1.14.99.50, in a competitive reaction containing 1 mM of each histidine, N-alpha-trimethylhistidine, and cysteine, OvoAErw-NW and EgtB(ovo) produce exclusively gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide. Because Erwinia tasmaniensis and most other OvoA encoding organisms do not encode an EgtD-type histidine methyltransferase, it seems clear that this N-alpha-trimethylhistidine-consuming side activity of OvoAErwin has no physiological purpose. Such promiscuity may have facilitated the transition of an ancestral sulfoxide synthase from ovothiol to erothioneine biosynthesis
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
-
enzyme OvoA belongs to the 2-His-1-carboxylate catalytic triad type of mononuclear non-heme iron enzymes
-
evolution
-
cyanobacterial OvoA homologues (Egt-B(ovo)) have evolved to catalyze an EgtB-type reaction by convergent evolution, cf. EC 1.14.99.50, in a competitive reaction containing 1 mM of each histidine, N-alpha-trimethylhistidine, and cysteine, OvoAErw-NW and EgtB(ovo) produce exclusively gamma-L-glutamyl-S-(hercyn-2-yl)-L-cysteine S-oxide
-
malfunction
mutation of the 2-His-1-carboxylate catalytic triad of the enzyme disrupts the cysteine dioxygenase activity
malfunction
-
mutation of any of the residues in the HX3HXE motif in OvoA results in an over 100fold attenuation of activity
malfunction
-
mutation of the 2-His-1-carboxylate catalytic triad of the enzyme disrupts the cysteine dioxygenase activity
-
metabolism
OvoA is an iron(II) dependent sulfoxide synthase which catalyzes the first step in ovothiol A biosynthesis
metabolism
the enzyme is involved in the ergothioneine and ovothiol biosynthesis. Besides catalyzing the oxidative coupling between histidine and cysteine, enzyme OvoA can also catalyze a direct oxidative coupling between hercynine and cysteine, which can shorten the ergothioneine biosynthetic pathway by two steps, overview
metabolism
OvoAis required in ovothiol biosynthesis catalyzing the oxidative coupling between histidine and cysteine
metabolism
-
enzyme OvoA is responsible for the oxidative C-S bond formation in ovothiol biosynthesis. OvoA in ovothiol biosynthesis has a relaxed substrate specificity
metabolism
gene ovoA is involved in ovothiol biosynthesis
metabolism
sulfoxide synthase OvoA catalyzes the formation of 5-histidylcysteine sulfoxide in the ovothiol biosynthesis. Short cyanobacterial OvoA-type enzymes may contribute to ergothioneine (EC 1.14.99.51) instead of ovothiol production
metabolism
-
sulfoxide synthase OvoA catalyzes the formation of 5-histidylcysteine sulfoxide in the ovothiol biosynthesis. Short cyanobacterial OvoA-type enzymes may contribute to ergothioneine (EC 1.14.99.51) instead of ovothiol production
metabolism
-
sulfoxide synthase OvoA catalyzes the formation of 5-histidylcysteine sulfoxide in the ovothiol biosynthesis. Short cyanobacterial OvoA-type enzymes may contribute to ergothioneine (EC 1.14.99.51) instead of ovothiol production
metabolism
-
OvoA is an iron(II) dependent sulfoxide synthase which catalyzes the first step in ovothiol A biosynthesis
-
metabolism
-
the enzyme is involved in the ergothioneine and ovothiol biosynthesis. Besides catalyzing the oxidative coupling between histidine and cysteine, enzyme OvoA can also catalyze a direct oxidative coupling between hercynine and cysteine, which can shorten the ergothioneine biosynthetic pathway by two steps, overview
-
metabolism
-
OvoAis required in ovothiol biosynthesis catalyzing the oxidative coupling between histidine and cysteine
-
metabolism
-
sulfoxide synthase OvoA catalyzes the formation of 5-histidylcysteine sulfoxide in the ovothiol biosynthesis. Short cyanobacterial OvoA-type enzymes may contribute to ergothioneine (EC 1.14.99.51) instead of ovothiol production
-
physiological function
ovothiol is proposed to be involved in H2O2 scavenging and facilitating the fertilization process
physiological function
the enzyme is the ovothiol biosynthetic enzyme, ovothiols are histidine-derived thiols
physiological function
-
the enzyme is the ovothiol biosynthetic enzyme, ovothiols are histidine-derived thiols
physiological function
crucial role of OvoA in protecting embryos released in seawater from environmental cues, thus allowing the survival under different conditions
physiological function
-
ovothiol is proposed to be involved in H2O2 scavenging and facilitating the fertilization process
-
physiological function
-
the enzyme is the ovothiol biosynthetic enzyme, ovothiols are histidine-derived thiols
-
additional information
the enzyme requires coordination of iron(II) to an unusual iron-binding motif
additional information
-
the enzyme requires coordination of iron(II) to an unusual iron-binding motif
additional information
-
residues in the HX3HXE motif are catalytically important (i.e., likely bind iron). Structure homology modeling, overview
additional information
enzyme structure modeling, excluding the C-terminal additional domain, overview
additional information
-
enzyme structure modeling, excluding the C-terminal additional domain, overview
additional information
an OvoA-like protein, full-length OvoA homologue, OvoA_1, with a C-terminal methyltransferase, most OvoAs contain a C-terminal methyltransferase
additional information
an OvoA-like protein, full-length OvoA homologue, OvoA_1, with a C-terminal methyltransferase, most OvoAs contain a C-terminal methyltransferase
additional information
homologue OvoA_2 is a monofunctional sulfoxide synthase without a C-terminal methyltransferase
additional information
homologue OvoA_2 is a monofunctional sulfoxide synthase without a C-terminal methyltransferase
additional information
-
the enzyme requires coordination of iron(II) to an unusual iron-binding motif
-
additional information
-
an OvoA-like protein, full-length OvoA homologue, OvoA_1, with a C-terminal methyltransferase, most OvoAs contain a C-terminal methyltransferase
-
additional information
-
homologue OvoA_2 is a monofunctional sulfoxide synthase without a C-terminal methyltransferase
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). A0A1D8U0C7_9CYAN
454
0
53007
TrEMBL
-
A0A1D8U386_9CYAN
717
0
81849
TrEMBL
-
B2VFD8_ERWT9
Erwinia tasmaniensis (strain DSM 17950 / CFBP 7177 / CIP 109463 / NCPPB 4357 / Et1/99)
719
0
82439
TrEMBL
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E176A
site-directed mutagenesis, the mutant shows reduced enzyme activity by at least 100fold compared to the wild-type enzyme
H170A
site-directed mutagenesis, the mutant shows reduced enzyme activity by at least 100fold compared to the wild-type enzyme
H174A
site-directed mutagenesis, the mutant shows reduced enzyme activity by at least 100fold compared to the wild-type enzyme
Y417F
barely any coupling product formation is found in the mutant
E176A
-
site-directed mutagenesis, the mutant shows reduced enzyme activity by at least 100fold compared to the wild-type enzyme
-
H170A
-
site-directed mutagenesis, the mutant shows reduced enzyme activity by at least 100fold compared to the wild-type enzyme
-
H174A
-
site-directed mutagenesis, the mutant shows reduced enzyme activity by at least 100fold compared to the wild-type enzyme
-
Y417F
-
barely any coupling product formation is found in the mutant
-
additional information
additional information
replacing active site Tyr417 with 2-amino-3-(4-hydroxy-3-(methylthio) phenyl) propanoic acid modulates the two OvoA activities (oxidative coupling between cysteine and histidine, and cysteine dioxygenase activity). In the variant, the ratio between S-(L-histidin-5-yl)-L-cysteine S-oxide and cysteine sulfinic acid changes from 9:1 in wild-type enzyme reaction to 7:3
additional information
-
replacing active site Tyr417 with 2-amino-3-(4-hydroxy-3-(methylthio) phenyl) propanoic acid modulates the two OvoA activities (oxidative coupling between cysteine and histidine, and cysteine dioxygenase activity). In the variant, the ratio between S-(L-histidin-5-yl)-L-cysteine S-oxide and cysteine sulfinic acid changes from 9:1 in wild-type enzyme reaction to 7:3
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant Strep-tagged enzyme from Escherichia coli by affinity chromatography
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene ovoA, multi-exonic gene with 18 exons, DNA and amino acid sequence analysis, sequence comparisons and phylogenetic analysis
gene ovoA, multi-exonic gene with 19 exons, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic analysis, quantitative real time PCR enzyme expression analysis
gene ovoA, recombinant expression of His-tagged enzyme in Escherichia coli
gene ovoA, the mutant enzyme loses the cysteine dioxygenase activity but also stops catalyzing the formation of oxidative coupling product
recombinant overexpression of Strep-tagged enzyme in Escherichia coli
gene ovoA, recombinant expression of His-tagged enzyme in Escherichia coli
gene ovoA, recombinant expression of His-tagged enzyme in Escherichia coli
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
at the pluteus stage PlOvoA mRNA is strongly downregulated after exposure to 0.005-0.010 mM Cd2+
PlOvoA embryo expression significantly increases at the pluteus stage and is upregulated by metals (Cd2+ and Mn2+) at concentrations mimicking polluted sea-water and by cyclic toxic algal blooms, leading to ovothiol biosynthesis. In silico analysis of the PlOvoA upstream region reveals metal and stress responsive elements. PlOvoA expression profile and response to environmental stress conditions, overview. A significant increase of PlOvoA mRNA is observed at the swimming blastula stage after exposure to 0.001-0.005 mM Cd2+, whereas at the early blastula and prism stages, the gene transcription is unaffected. On the contrary, at the pluteus stage PlOvoA mRNA is strongly down-regulated after exposure to 0.005-0.010 mM Cd2+. In the presence of Mn2+, the relative expression ratio of PlOvoA at the swimming blastula stage is close to the minimum value considered significant. No appreciable gene regulation is observed in other developmental stages
SpOvoA upstream region analysis reveals several metal and stress responsive elements, overview
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
synthesis
potential application of the oxidative coupling between hercynine and cysteine for industrial ergothioneine production
synthesis
-
the ergothioneine biosynthetic pathway (EgtA-EgtE catalysis) provides an opportunity for ergothioneine production through metabolic engineering, but the kinetic properties and the presence of side-reaction render OvoA not suitable for use in ergothioneine production through metabolic engineering
synthesis
-
potential application of the oxidative coupling between hercynine and cysteine for industrial ergothioneine production
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mashabela, G.T.; Seebeck, F.P.
Substrate specificity of an oxygen dependent sulfoxide synthase in ovothiol biosynthesis
Chem. Commun. (Camb. )
49
7714-7716
2013
Erwinia tasmaniensis (B2VFD8), Erwinia tasmaniensis DSM 17950 (B2VFD8)
brenda
Bushnell, E.A.; Fortowsky, G.B.; Gauld, J.W.
Model iron-oxo species and the oxidation of imidazole: insights into the mechanism of OvoA and EgtB?
Inorg. Chem.
51
13351-13356
2012
Erwinia tasmaniensis (B2VFD8), Erwinia tasmaniensis DSM 17950 (B2VFD8)
brenda
Braunshausen, A.; Seebeck, F.P.
Identification and characterization of the first ovothiol biosynthetic enzyme
J. Am. Chem. Soc.
133
1757-1759
2011
Erwinia tasmaniensis (B2VFD8), Erwinia tasmaniensis DSM 17950 (B2VFD8), Trypanosoma cruzi
brenda
Song, H.; Leninger, M.; Lee, N.; Liu, P.
Regioselectivity of the oxidative C-S bond formation in ergothioneine and ovothiol biosyntheses
Org. Lett.
15
4854-4857
2013
Erwinia tasmaniensis (B2VFD8), Erwinia tasmaniensis DSM 17950 (B2VFD8)
brenda
Song, H.; Her, A.S.; Raso, F.; Zhen, Z.; Huo, Y.; Liu, P.
Cysteine oxidation reactions catalyzed by a mononuclear non-heme iron enzyme (OvoA) in ovothiol biosynthesis
Org. Lett.
16
2122-2125
2014
Erwinia tasmaniensis (B2VFD8), Erwinia tasmaniensis DSM 17950 (B2VFD8)
brenda
Hu, W.; Song, H.; Sae Her, A.; Bak, D.W.; Naowarojna, N.; Elliott, S.J.; Qin, L.; Chen, X.; Liu, P.
Bioinformatic and biochemical characterizations of C-S bond formation and cleavage enzymes in the fungus Neurospora crassa ergothioneine biosynthetic pathway
Org. Lett.
16
5382-5385
2014
Erwinia tasmaniensis
brenda
Liao, C.; Seebeck, F.P.
Convergent evolution of ergothioneine biosynthesis in cyanobacteria
ChemBioChem
18
2115-2118
2017
Erwinia tasmaniensis, Microcystis aeruginosa, Moorena producens (A0A1D8U386), Moorena producens (A0A1D8U0C7), Moorena producens PAL-8-15-08-1 (A0A1D8U386), Moorena producens PAL-8-15-08-1 (A0A1D8U0C7)
brenda
Peck, S.C.; van der Donk, W.A.
Go it alone four-electron oxidations by mononuclear non-heme iron enzymes
J. Biol. Inorg. Chem.
22
381-394
2017
Erwinia tasmaniensis
brenda
Castellano, I.; Migliaccio, O.; D'Aniello, S.; Merlino, A.; Napolitano, A.; Palumbo, A.
Shedding light on ovothiol biosynthesis in marine metazoans
Sci. Rep.
6
21056
2016
Paracentrotus lividus (A0A140GAV9), Paracentrotus lividus, Strongylocentrotus purpuratus (A0A7M7PQ98)
brenda
Chen, L.; Naowarojna, N.; Song, H.; Wang, S.; Wang, J.; Deng, Z.; Zhao, C.; Liu, P.
Use of a tyrosine analogue to modulate the two activities of a nonheme iron enzyme OvoA in ovothiol biosynthesis, cysteine oxidation versus oxidative C-S bond formation
J. Am. Chem. Soc.
140
4604-4612
2018
Erwinia tasmaniensis (B2VFD8), Erwinia tasmaniensis DSM 17950 (B2VFD8)
brenda
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