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Information on EC 4.1.3.44 - tRNA 4-demethylwyosine synthase (AdoMet-dependent)
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EC Tree
4.1.3.44 tRNA 4-demethylwyosine synthase (AdoMet-dependent)IUBMB Comments
This enzyme, which is a member of the superfamily of S-adenosyl-L-methionine-dependent radical (radical AdoMet) enzymes, binds two [4Fe-4S] clusters [3,4]. Carbons C2 and C3 from pyruvate are incorporated into 4-demethylwyosine . The enzyme is found in eukaryotes where it is part of the pathway for wybutosine synthesis, and in archaea, where it is involved in the biosynthesis of archaeal wye bases, such as wyosine, isowyosine, and methylwyosine.
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Word Map
- 4.1.3.44
- wybutosine
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decoding
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anticodon
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tricyclic
- guanosine
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codon-anticodon
- s-adenosyl-l-methionine
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5\'-deoxyadenosyl
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3'-position
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iron-sulfur
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
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N1-methylguanine37 in tRNAPhe
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Synonyms
ypl207w, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Taw1
tRNA wyosine derivatives biosynthesis protein Taw1
TYW1
YPL207W
tRNA wyosine derivatives biosynthesis protein Taw1
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TYW1
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine = 4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
tRNAPhe N1-methylguanine,pyruvate acetaldehyde-lyase (tRNAPhe 4-demethylwyosine-forming, decarboxylating, dehydrating)
This enzyme, which is a member of the superfamily of S-adenosyl-L-methionine-dependent radical (radical AdoMet) enzymes, binds two [4Fe-4S] clusters [3,4]. Carbons C2 and C3 from pyruvate are incorporated into 4-demethylwyosine [3]. The enzyme is found in eukaryotes where it is part of the pathway for wybutosine synthesis, and in archaea, where it is involved in the biosynthesis of archaeal wye bases, such as wyosine, isowyosine, and methylwyosine.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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ir
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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?
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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ir
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
enzyme catalyzes the condensation of N-methylguanosine with two carbon atoms from pyruvate to form 4-demethylwyosine, which is a common intermediate in the biosynthesis of all of the hypermodified RNA bases related to wybutosine. C2 and C3 of pyruvate are incorporated while C1 is not
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N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
enzyme catalyzes the condensation of N-methylguanosine with two carbon atoms from pyruvate to form 4-demethylwyosine, which is a common intermediate in the biosynthesis of all of the hypermodified RNA bases related to wybutosine. C2 and C3 of pyruvate are incorporated while C1 is not
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N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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ir
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
Pyrococcus abyssi GE5 / CNCM I-1302 / DSM 25543
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additional information
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the conserved Lys residue forms a Schiff base with pyruvate. Reductive cleavage of SAM leads to formation of dAdo radical, which propagates the radical to the m1G generating a substrate radical. Radical addition to C-2 of pyruvate followed by homolytic scission of the C-1-C-2 bond would generate an intermediate, which through transimmination and subsequent deprotonation, forms imG-14. The resulting formyl radical can either acquire an H-atom or undergo reduction and protonation to produce formate. Alternatively, oxidation of the formyl radical would generate CO2
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additional information
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the conserved Lys residue forms a Schiff base with pyruvate. Reductive cleavage of SAM leads to formation of dAdo radical, which propagates the radical to the m1G generating a substrate radical. Radical addition to C-2 of pyruvate followed by homolytic scission of the C-1-C-2 bond would generate an intermediate, which through transimmination and subsequent deprotonation, forms imG-14. The resulting formyl radical can either acquire an H-atom or undergo reduction and protonation to produce formate. Alternatively, oxidation of the formyl radical would generate CO2
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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ir
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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ir
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
enzyme catalyzes the condensation of N-methylguanosine with two carbon atoms from pyruvate to form 4-demethylwyosine, which is a common intermediate in the biosynthesis of all of the hypermodified RNA bases related to wybutosine. C2 and C3 of pyruvate are incorporated while C1 is not
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?
N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
enzyme catalyzes the condensation of N-methylguanosine with two carbon atoms from pyruvate to form 4-demethylwyosine, which is a common intermediate in the biosynthesis of all of the hypermodified RNA bases related to wybutosine. C2 and C3 of pyruvate are incorporated while C1 is not
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N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine
4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O
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ir
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Fe-S center
residues Cys81, Cys85 and Cys88 are predicted to comprise the iron-sulfur cluster. In the crystal structure, their side chains face each other to create the cluster site
[4Fe-4S]-center
the N-terminal half of the enzyme beside the radical-SAM cysteine triad, contains an additional highly conserved cysteine motif involved in the coordination of a second [4Fe-4S] cluster. This cluster displays a free coordination site that interacts with pyruvate, the second substrate of the reaction
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Iron
protein contains contained up to 8.2 iron and 8.2 sulfide ions per polypeptide chain
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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
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
genes YPL207w, YML005w, YGL050w and YOL141w, named TYW1, TYW2, TYW3 and TYW4, respectively are essential for wybutosine synthesis. TYW1 is an iron-sulfur (Fe-S) cluster protein responsible for the tricyclic formation
physiological function
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genes YPL207w, YML005w, YGL050w and YOL141w, named TYW1, TYW2, TYW3 and TYW4, respectively are essential for wybutosine synthesis. TYW1 is an iron-sulfur (Fe-S) cluster protein responsible for the tricyclic formation
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Show AA Sequence and Transmembrane Helices (4452 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 100 mM KH2PO4/Na2HPO4 pH 6.2, 10% (w/v) PEG 3000
to 2.4 A resolution. Enzyme TYW1 assumes an incomplete TIM barrel with (alpha/beta)6 topology, which closely resembles the reported structures of radical SAM enzymes. TYW1 is considered to catalyze the cyclization reaction by utilizing the radical intermediate. construction of a model structure complexed with S-adenosylmethionine and two [4Fe-4S] clusters
to 2.2 A resolution. The overall structure is a half-barrel structure, composed of six alpha-helices packed against a ten-stranded beta-sheet. Other alpha-helices and two long loops form the walls on both sides of the half-barrel. Construction of a docking model with the FeS clusters, AdoMet and the tRNA
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C195S
the mutant shows reduced activity compared tot he wild type enzyme
C195S
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the mutant shows reduced activity compared tot he wild type enzyme
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C479A
mutation in the conserved C479xxxC483xxC486 motif of the radical-Ado-Met domain, complete loss of activity
C483A
mutation in the conserved C479xxxC483xxC486 motif of the radical-Ado-Met domain, complete loss of activity
C486A
mutation in the conserved C479xxxC483xxC486 motif of the radical-Ado-Met domain, complete loss of activity
E532A
mutation in a candidate GGE motif in the radical Ado-Met domain, no loss of activity
E550A
C479A
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mutation in the conserved C479xxxC483xxC486 motif of the radical-Ado-Met domain, complete loss of activity
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C483A
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mutation in the conserved C479xxxC483xxC486 motif of the radical-Ado-Met domain, complete loss of activity
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C486A
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mutation in the conserved C479xxxC483xxC486 motif of the radical-Ado-Met domain, complete loss of activity
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E532A
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mutation in a candidate GGE motif in the radical Ado-Met domain, no loss of activity
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E550A
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mutation in a candidate GGE motif in the radical Ado-Met domain, complete loss of activity
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E550A
mutation in a candidate GGE motif in the radical Ado-Met domain, complete loss of activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, butyl Sepharose column chromatography, and HiTrap chelating column chromatography
ammonium sulfate precipitation, HiTrap chealting column chromatography, and butyl Sepharose column chromatography
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purified anaerobically and reconstituted with Fe and S. The reconstituted protein is brown and has an absorbance spectrum that displays a characteristic shoulder at 400 nm
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Noma, A.; Kirino, Y.; Ikeuchi, Y.; Suzuki, T.
Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA
EMBO J.
25
2142-2154
2006
Saccharomyces cerevisiae (Q08960), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 (Q08960)
brenda
Goto-Ito, S.; Ishii, R.; Ito, T.; Shibata, R.; Fusatomi, E.; Sekine, S.I.; Bessho, Y.; Yokoyama, S.
Structure of an archaeal TYW1, the enzyme catalyzing the second step of wye-base biosynthesis
Acta Crystallogr. Sect. D
63
1059-1068
2007
Pyrococcus horikoshii (O59412), Pyrococcus horikoshii DSM 12428 (O59412)
brenda
Young, A.P.; Bandarian, V.
Pyruvate is the source of the two carbons that are required for formation of the imidazoline ring of 4-demethylwyosine
Biochemistry
50
10573-10575
2011
Methanocaldococcus jannaschii (Q57705), Methanocaldococcus jannaschii ATCC 43067 (Q57705)
brenda
Perche-Letuvee, P.; Kathirvelu, V.; Berggren, G.; Clemancey, M.; Latour, J.M.; Maurel, V.; Douki, T.; Armengaud, J.; Mulliez, E.; Fontecave, M.; Garcia-Serres, R.; Gambarelli, S.; Atta, M.
4-Demethylwyosine synthase from Pyrococcus abyssi is a radical-S-adenosyl-L-methionine enzyme with an additional [4Fe-4S](+2) cluster that interacts with the pyruvate co-substrate
J. Biol. Chem.
287
41174-41185
2012
Pyrococcus abyssi (Q9V1F9), Pyrococcus abyssi, Pyrococcus abyssi GE5 / CNCM I-1302 / DSM 25543 (Q9V1F9)
brenda
Suzuki, Y.; Noma, A.; Suzuki, T.; Senda, M.; Senda, T.; Ishitani, R.; Nureki, O.
Crystal structure of the radical SAM enzyme catalyzing tricyclic modified base formation in tRNA
J. Mol. Biol.
372
1204-1214
2007
Saccharomyces cerevisiae (Q08960), Methanocaldococcus jannaschii (Q57705), Methanocaldococcus jannaschii DSM 2661 (Q57705), Saccharomyces cerevisiae ATCC 204508 (Q08960)
brenda
Young, A.; Bandarian, V.
Mechanistic studies of the radical S-adenosyl-L-methionine enzyme 4-demethylwyosine synthase reveal the site of hydrogen atom abstraction
Biochemistry
54
3569-3572
2015
Methanocaldococcus jannaschii
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brenda
Kathirvelu, V.; Perche-Letuvee, P.; Latour, J.; Atta, M.; Forouhar, F.; Gambarelli, S.; Garcia-Serres, R.
Spectroscopic evidence for cofactor-substrate interaction in the radical-SAM enzyme TYW1
Dalton Trans.
46
13211-13219
2017
Methanocaldococcus jannaschii (Q57705)
brenda
Grell, T.; Young, A.; Drennan, C.; Bandarian, V.
Biochemical and structural characterization of a Schiff Base in the radical-mediated biosynthesis of 4-demethylwyosine by TYW1
J. Am. Chem. Soc.
140
6842-6852
2018
Methanocaldococcus jannaschii (Q57705), Methanocaldococcus jannaschii DSM 2661 (Q57705)
brenda
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