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Information on EC 2.4.2.60 - cysteine-dependent adenosine diphosphate thiazole synthase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P32318

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IUBMB Comments
This iron dependent enzyme, found in fungi, plants, and some archaea, is involved in the thiamine phosphate biosynthesis pathway. It is a single turn-over enzyme since the cysteine residue is not regenerated in vivo . The homologous enzyme in archaea (EC 2.4.2.59, sulfide-dependent adenosine diphosphate thiazole synthase) uses sulfide as sulfur donor.
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Saccharomyces cerevisiae
UNIPROT: P32318
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The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Reaction Schemes
hide
NAD+
+
glycine
+
[ADP-thiazole synthase]-L-cysteine
=
nicotinamide
+
ADP-5-ethyl-4-methylthiazole-2-carboxylate
+
[ADP-thiazole synthase]-dehydroalanine
+
3
H2O
+
+
[ADP-thiazole synthase]-L-cysteine
=
+
+
[ADP-thiazole synthase]-dehydroalanine
+
3
Synonyms
cypbp37, thi-4, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ADP-thiazole synthase
-
-
-
-
THI1
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
NAD+:glycine ADP-D-ribosyltransferase (dehydroalanine-producing)
This iron dependent enzyme, found in fungi, plants, and some archaea, is involved in the thiamine phosphate biosynthesis pathway. It is a single turn-over enzyme since the cysteine residue is not regenerated in vivo [3]. The homologous enzyme in archaea (EC 2.4.2.59, sulfide-dependent adenosine diphosphate thiazole synthase) uses sulfide as sulfur donor.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
NAD+ + glycine + [ADP-thiazole synthase]-L-cysteine
nicotinamide + ADP-5-ethyl-4-methylthiazole-2-carboxylate + [ADP-thiazole synthase]-dehydroalanine + 3 H2O
show the reaction diagram
-
-
-
?
NAD+ + glycine + [ADP-thiazole synthase]-L-cysteine
nicotinamide + ADP-5-ethyl-4-methylthiazole-2-carboxylate + [ADP-thiazole synthase]-dehydroalanine + 3 H2O
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NAD+ + glycine + [ADP-thiazole synthase]-L-cysteine
nicotinamide + ADP-5-ethyl-4-methylthiazole-2-carboxylate + [ADP-thiazole synthase]-dehydroalanine + 3 H2O
show the reaction diagram
-
-
-
?
NAD+ + glycine + [ADP-thiazole synthase]-L-cysteine
nicotinamide + ADP-5-ethyl-4-methylthiazole-2-carboxylate + [ADP-thiazole synthase]-dehydroalanine + 3 H2O
show the reaction diagram
-
-
-
?
additional information
?
-
Thi4 is a suicidal enzyme undergoing only a single turnover
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
iron-dependent sulfide transfer reaction from the protein to a reaction intermediate
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
protein Thi4 from Saccharomyces cerevisiae fails to catalyze the formation of the thiazole moiety from cysteine (or sulfide), glycine and a variety of C5 carbohydrates. Thi4 also fails to complement an Escherichia coli thiazole biosynthetic mutant ThiF. The ADP adduct of 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid is present at the active site of Thi4 and the carboxylic acid of the thiazole forms hydrogen bonding and electrostatic interactions with Arg301
physiological function
-
an enzyme deletion mutant displays increased sensitivity to oxidative stress and enhanced thiamine diphosphate biosynthesis as compared with the wild-type strain
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure of mutant C205S with a bound glycine imine intermediate. Comparison with structures of Methanococcus jannaschii and Methanococcus igneus homologues
to 1.8 A resolution. Thi4 exists as an octamer with two monomers in the asymmetric unit. A tightly bound adenosine diphospho-5-(beta-ethyl)-4-methylthiazole-2-carboxylic acid is present at the active site. The Thi4 structure reveals a protein structure with a GR2 domain that binds NAD instead of FAD
C205S variant with a bound glycine imine intermediate, hanging drop vapor diffusion method, using 25% (w/v) PEG1500, 0.0125 M succinic acid, 0.044 M sodium dihydrogen phosphate, and 0.044 M glycine, pH 8.5
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C204A
H200N
C205S
the mutant is catalytic in the presence of exogenous sulfide
H237N
the mutant only catalyzes the conversion of ADP-ribose to ADP-ribulose
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is completely repressed throughout batch culture by thiamine at a concentration around 1 microM, but high level constitutive expression occurs in thiamine-free medium
-
expression is induced by to oxidative and osmotic stress
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expression is induced when the intracellular concentration of thiamine falls to 20 pmol per 10 million cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jurgenson, C.; Chatterjee, A.; Begley, T.; Ealick, S.
Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiae
Biochemistry
45
11061-11070
2006
Saccharomyces cerevisiae (P32318), Saccharomyces cerevisiae ATCC 204508 (P32318)
Manually annotated by BRENDA team
Zhang, X.; Eser, B.; Chanani, P.; Begley, T.; Ealick, S.
Structural basis for iron-mediated sulfur transfer in archael and yeast thiazole synthases
Biochemistry
55
1826-1838
2016
Methanocaldococcus igneus, Methanocaldococcus jannaschii (Q58018), Methanocaldococcus jannaschii DSM 2661 (Q58018), Saccharomyces cerevisiae, Saccharomyces cerevisiae (P32318), Saccharomyces cerevisiae ATCC 204508 (P32318)
Manually annotated by BRENDA team
Kowalska, E.; Kujda, M.; Wolak, N.; Kozik, A.
Altered expression and activities of enzymes involved in thiamine diphosphate biosynthesis in Saccharomyces cerevisiae under oxidative and osmotic stress
FEMS Yeast Res.
12
534-546
2012
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Chatterjee, A.; Jurgenson, C.; Schroeder, F.; Ealick, S.; Begley, T.
Thiamin biosynthesis in eukaryotes Characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis
J. Am. Chem. Soc.
128
7158-7159
2006
Saccharomyces cerevisiae (P32318), Saccharomyces cerevisiae ATCC 204508 (P32318)
Manually annotated by BRENDA team
Chatterjee, A.; Jurgenson, C.; Schroeder, F.; Ealick, S.; Begley, T.
Biosynthesis of thiamin thiazole in eukaryotes Conversion of NAD to an advanced intermediate
J. Am. Chem. Soc.
129
2914-2922
2007
Saccharomyces cerevisiae (P32318)
Manually annotated by BRENDA team
Chatterjee, A.; Abeydeera, N.; Bale, S.; Pai, P.; Dorrestein, P.; Russell, D.; Ealick, S.; Begley, T.
Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase
Nature
478
542-546
2011
Saccharomyces cerevisiae (P32318)
Manually annotated by BRENDA team
Praekelt, U.; Byrne, K.; Meacock, P.
Regulation of THI4(MOL1), a thiamine-biosynthetic gene of Saccharomyces cerevisiae
Yeast
10
481-490
1994
Saccharomyces cerevisiae, Saccharomyces cerevisiae PMY3
Manually annotated by BRENDA team