Information on EC 2.1.1.148 - thymidylate synthase (FAD)

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The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota, dsDNA viruses, no RNA stage

EC NUMBER
COMMENTARY
2.1.1.148
-
RECOMMENDED NAME
GeneOntology No.
thymidylate synthase (FAD)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
5,10-methylenetetrahydrofolate + dUMP + NADPH + H+ = dTMP + tetrahydrofolate + NADP+
show the reaction diagram
FMN can replace FAD, reaction shown is distinct from that of the classical thymidylate synthase, ThyA (EC 2.1.1.45)
-
-
-
5,10-methylenetetrahydrofolate + dUMP + NADPH + H+ = dTMP + tetrahydrofolate + NADP+
show the reaction diagram
a hydride equivalent is transferred from the reduced flavin cofactor directly to the uracil ring, followed by an isomerization of the intermediate to form the product, 2'-deoxythymidine-5'-monophosphate
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
reductive methylation
-
proposed kinetic mechanisms for FDTS
reductive methylation
-
proposed kinetic mechanisms for FDTS
reductive methylation
-
proposed kinetic mechanisms for FDTS
reductive methylation
Rhodobacter capsulatus MT1131
-
proposed kinetic mechanisms for FDTS
-
PATHWAY
KEGG Link
MetaCyc Link
Metabolic pathways
-
One carbon pool by folate
-
pyrimidine deoxyribonucleotides de novo biosynthesis III
-
Pyrimidine metabolism
-
SYSTEMATIC NAME
IUBMB Comments
5,10-methylenetetrahydrofolate,FADH2:dUMP C-methyltransferase
Contains FAD. All thymidylate synthases catalyse a reductive methylation involving the transfer of the methylene group of 5,10-methylenetetrahydrofolate to the C5 position of dUMP and a two electron reduction of the methylene group to a methyl group. Unlike the classical thymidylate synthase, ThyA (EC 2.1.1.45), which uses folate as both a 1-carbon donor and a source of reducing equivalents, this enzyme uses a flavin coenzyme as a source of reducing equivalents, which are derived from NADPH.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
complementing thymidylate synthase
Q9WYT0
-
complementing thymidylate synthase
Thermotoga maritima TM0449
Q9WYT0
-
-
complementing thymidylate synthase
-
-
FDTS
Paramecium bursaria Chlorella virus-1, Pyrococcus furiosus, Rickettsia sp.
-
-
FDTS
Q9WYT0
-
FDTS
Thermotoga maritima ATCC 43589
Q9WYT0
-
-
FDTS
Treponema palladium
-
-
flavin dependent thymidylate synthase
-
-
flavin dependent thymidylate synthase
Paramecium bursaria Chlorella virus-1
-
-
flavin dependent thymidylate synthase
-
-
flavin-dependent thymidylate synthase
-
-
flavin-dependent thymidylate synthase
-
-
flavin-dependent thymidylate synthase
-
-
-
flavin-dependent thymidylate synthase
-
-
flavin-dependent thymidylate synthase
-
-
flavin-dependent thymidylate synthase
Paramecium bursaria Chlorella virus-1, Pyrococcus furiosus
-
-
flavin-dependent thymidylate synthase
Q8U3C9
-
flavin-dependent thymidylate synthase
-
-
flavin-dependent thymidylate synthase
Q9WYT0
-
flavin-dependent thymidylate synthase
Thermotoga maritima ATCC 43589
Q9WYT0
-
-
flavin-dependent thymidylate synthase
Treponema palladium
-
-
flavin-dependent thymidylate synthase X
-
-
flavin-dependent thymidylate synthase X
Rhodobacter capsulatus MT1131
-
-
-
flavin-dependent TS
-
-
Thy1
-
-
-
-
Thy1
Q8U3C9
-
thymidylate synthase 1
Q8U3C9
-
thymidylate synthase complementing protein
-
-
-
-
thymidylate synthase ThyX
Paramecium bursaria Chlorella virus-1
-
-
thymidylate synthase X
-
-
thymidylate synthase X
Q5UVJ4
-
thymidylate synthase X
Q5UVJ4
-
-
thymidylate synthase X
Q41156
-
ThyX
-
-
-
-
ThyX
Q5UVJ4
-
ThyX
Q5UVJ4
-
-
ThyX
Paramecium bursaria Chlorella virus-1
-
-
ThyX
Rhodobacter capsulatus MT1131
-
-
-
thyX-encoded thymidylate synthase
-
-
TSCP
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9031-61-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
enzyme found in three different species
-
-
Manually annotated by BRENDA team
Clostridium difficile
-
-
-
Manually annotated by BRENDA team
; simultaneous occurrence of thyA and thyX
-
-
Manually annotated by BRENDA team
; simultaneous occurrence of thyA and thyX
-
-
Manually annotated by BRENDA team
no activity in Archaeoglobus fulgidus
-
-
-
Manually annotated by BRENDA team
no activity in Corynebacterium glutamicum strain NCHU 87078
-
-
-
Manually annotated by BRENDA team
no activity in Homo sapiens
-
-
-
Manually annotated by BRENDA team
no activity in Methanocaldococcus jannaschii
-
-
-
Manually annotated by BRENDA team
no activity in Methanopyrus kandleri
AV19
-
-
Manually annotated by BRENDA team
no activity in Methanopyrus kandleri AV19
AV19
-
-
Manually annotated by BRENDA team
no activity in Methanothermobacter thermoautotrophicus
-
-
-
Manually annotated by BRENDA team
Paramecium bursaria Chlorella virus-1
-
-
-
Manually annotated by BRENDA team
DSM3638
SwissProt
Manually annotated by BRENDA team
strain MT1131
-
-
Manually annotated by BRENDA team
Rhodobacter capsulatus MT1131
strain MT1131
-
-
Manually annotated by BRENDA team
; TM0449
SwissProt
Manually annotated by BRENDA team
enzyme additionally shows oxidase activity
SwissProt
Manually annotated by BRENDA team
TM0449
SwissProt
Manually annotated by BRENDA team
Thermotoga maritima ATCC 43589
-
SwissProt
Manually annotated by BRENDA team
Thermotoga maritima TM0449
TM0449
SwissProt
Manually annotated by BRENDA team
Treponema palladium
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
DNA replication speed in bacteria and archaea that contain the low-activity ThyX enzyme is up to 10fold decreased compared with species that contain the catalytically more efficient ThyA, EC 2.1.1.45. Both ThyX and ThyA participate in frequent reciprocal gene replacement events. The bacterial metabolism continues to modulate the size and composition of prokaryotic genomes. The increased kinetic efficiency of thymidylate synthesis may have contributed to extending the prokaryotic evolutionary potential
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5,10-methylenetetrahydrofolate + BrdUMP + FADH2
?
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Clostridium difficile
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Clostridium difficile
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9UZ51
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Paramecium bursaria Chlorella virus-1
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q41156
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q5UVJ4
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
de novo synthesis of thymidylate
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
de novo synthesis of thymidylate
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9UZ51
de novo synthesis of thymidylate
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
the flavin is oxidized after dUMP reacts with 5,10-methylenetetrahydrofolate
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
dUMP dependent lag-phase for the single turnover reduction of FDTS bound FAD by NADPH
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
Rhodobacter capsulatus ThyX is required for de novo thymidylate synthesis
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Rhodobacter capsulatus MT1131
-
-, Rhodobacter capsulatus ThyX is required for de novo thymidylate synthesis
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Thermotoga maritima TM0449
Q9WYT0
-
-
-
-, ?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Thermotoga maritima TM0449
Q9WYT0
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q5UVJ4
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Thermotoga maritima ATCC 43589
Q9WYT0
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2 + O2
dTMP + tetrahydrofolate + FAD + H2O2
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FMNH2
dTMP + tetrahydrofolate + FMN
show the reaction diagram
Q9WYT0
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FMNH2
dTMP + tetrahydrofolate + FMN
show the reaction diagram
Q9UZ51
-
-
?
5,10-methylenetetrahydrofolate + dUMP + NADPH
dTMP + tetrahydrofolate + NADP
show the reaction diagram
-
-, Rhodobacter capsulatus ThyX is required for de novo thymidylate synthesis
-
-
?
additional information
?
-
Q9WYT0
the enzyme is essential to DNA replication
-
-
-
additional information
?
-
Paramecium bursaria Chlorella virus-1
-
oxidation of NAD(P)H is linked to the reduction of enzyme bound FAD, dUMP is required for efficient FAD reduction, omitting of 5,10-methylenetetrahydrofolate from reaction mixture increases oxidation activity by a factor of 7
-
-
-
additional information
?
-
-
mRNA binding traits
-
-
-
additional information
?
-
-, Q8U3C9
possesses RNA-binding activity, binds to the stem–loop RNA structure
-
-
-
additional information
?
-
Q9WYT0
flavin-dependent thymidylate synthase can function as an oxidase, which catalyzes the reduction of O2 to H2O2, using reduced NADPH or other reducing agents and a sequential kinetic mechanism of substrate binding. Tetrahydrofolate competitively inhibits the oxidase activity, which indicates that tetrahydrofolate and O2 compete for the same reduced and dUMP-activated enzymatic complex
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q41156
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
-
de novo synthesis of thymidylate
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9WYT0
de novo synthesis of thymidylate
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Q9UZ51
de novo synthesis of thymidylate
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Rhodobacter capsulatus, Rhodobacter capsulatus MT1131
-
Rhodobacter capsulatus ThyX is required for de novo thymidylate synthesis
-
-
?
5,10-methylenetetrahydrofolate + dUMP + FADH2
dTMP + tetrahydrofolate + FAD
show the reaction diagram
Thermotoga maritima TM0449
Q9WYT0
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP + FADH2 + O2
dTMP + tetrahydrofolate + FAD + H2O2
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP + NADPH
dTMP + tetrahydrofolate + NADP
show the reaction diagram
-
Rhodobacter capsulatus ThyX is required for de novo thymidylate synthesis
-
-
?
additional information
?
-
Q9WYT0
the enzyme is essential to DNA replication
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
FAD
-
tightly bound, four molecules per tetramer
FAD
-
tightly bound, four molecules per tetramer
FAD
Q9WYT0
even though FAD is very well bound to three subunits, FAD interactions are not an absolute requirement for tetramer stabilization; tightly bound, four molecules per tetramer
FAD
Q9WYT0
the pro-R hydride of NADPH and not the R6 hydride of the tetrahydropterin is the reducing agent. The stereospecificity for the pro-R NADPH oxidation is not absolute. The hydride is transferred to FAD, which is the rate-limiting step of the catalytic cascade
FAD
-
the flavin is oxidized after dUMP reacts with 5,10-methylenetetrahydrofolate
FAD
Paramecium bursaria Chlorella virus-1
-
noncovalently bound
FAD
-
wild-type and mutant enzymes Y87F, S84Y, H48Q, S84A and S84C contain quantities of tightly bound FAD. Mutant enzymes R74A, R74K, H48Q/S84A and H48Q/S84C easily lose considerable amounts of bound FAD
FAD
Paramecium bursaria Chlorella virus-1
-
-
FAD
no activity in Corynebacterium glutamicum strain NCHU 87078
-
-
FAD
Q5UVJ4
the enzyme is bound to 4 FAD molecules
FADH2
-
activity is dependent on reduced flavin nucleotides
FADH2
-
the flavin is oxidized after dUMP reacts with 5,10-methylenetetrahydrofolate
FMNH2
-
activity is dependent on reduced flavin nucleotides
NAD(P)H
Q9WYT0
required
NADH
Paramecium bursaria Chlorella virus-1
-
oxidation of NADH is linked to the reduction of enzyme bound FAD, dUMP is required for efficient FAD reduction, omitting of 5,10-methylenetetrahydrofolate from reaction mixture increases oxidation activity by a factor of 7
NADP+
-
expulsion of the cofactor FAD by NADP+, no anticipated ThyX-FAD-BrdUMP-NADP+ quaternary complex, but a ThyX-NADP+ binary complex
NADPH
Q9WYT0
the pro-R hydride of NADPH and not the R6 hydride of the tetrahydropterin is the reducing agent. The stereospecificity for the pro-R NADPH oxidation is not absolute. The hydride is transferred to FAD, which is the rate-limiting step of the catalytic cascade
NADPH
Paramecium bursaria Chlorella virus-1
-
oxidation of NADPH is linked to the reduction of enzyme bound FAD, dUMP is required for efficient FAD reduction, omitting of 5,10-methylenetetrahydrofolate from reaction mixture increases oxidation activity by a factor of 7
NADPH
Paramecium bursaria Chlorella virus-1
-
residue His53 is crucial for NADPH oxidation, is located in the vicinity of the redox active N-5 atom of the FAD ring system
NADPH
Q41156
FAD/NAPDH couple
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mn2+
-, Q8U3C9
0.5 mM enhances the activity
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(heptanoyl[[(4R)-2-phenyl-3-(phenylcarbonyl)-1,3-thiazolidin-4-yl]methyl] amino)acetic acid
Q41156
-
10-methyl-5,8-dideazafolate
Paramecium bursaria Chlorella virus-1
-
0.2 mM, 90% inhibition
10-propargylfolate
Paramecium bursaria Chlorella virus-1
-
0.2 mM, 85% inhibition
5,10-methylenetetrahydrofolate
Paramecium bursaria Chlorella virus-1
-
-
5-fluoro-2'-deoxyuridine 5'-monophosphate
-
FdUMP
5-fluorodeoxyuridine
Paramecium bursaria Chlorella virus-1
-
0.05 mM, 95% inhibition
8-aminopurinone deoxyribonucleoside 5'-phosphate
Paramecium bursaria Chlorella virus-1
-
0.05 mM, 50% inhibition
diethyldicarbonate
Paramecium bursaria Chlorella virus-1
-
decreases ThyX deprotonation activity at least 20fold, is partially reversible with hydroxylamine treatment
ethyl (4R)-2-phenyl-3-([(1-(3-2,2,2-trifluoroacetamido)propyl)-1H-1,2,3-triazol-4-yl]carbonyl)-1,3-thiazolidine-4-carboxylate
Q41156
-
ethyl (4R)-2-phenyl-3-[[1-(2-thiophen-3-ylethyl)-1H-1,2,3-triazol-4-yl]carbonyl]-1,3-thiazolidine-4-carboxylate
Q41156
-
ethyl (4R)-3-([1-[2-(4-fluorophenyl)ethyl]-1H-1,2,3-triazol-4-yl]carbonyl)-2-phenyl-1,3-thiazolidine-4-carboxylate
Q41156
-
ethyl (4R)-3-[[1-(7-hydroxyheptyl)-1H-1,2,3-triazol-4-yl]carbonyl]-2-phenyl-1,3-thiazolidine-4-carboxylate
Q41156
-
NADPH
-
inhibits FDTS at high concentrations at all temperatures, NADPH may not be the natural reducing agent of FDTS
NADPH
Q5UVJ4
excess NADPH decreases enzyme activity
tetrahydrofolate
Q9WYT0
competitively inhibits the oxidase activity of the enzyme, which indicates that tetrahydrofolate and O2 compete for the same reduced and dUMP-activated enzymatic complex
additional information
Paramecium bursaria Chlorella virus-1
-
no inhibition by 10-propargyl-5,6-dideazafolate, 10-methylfolate, 8-azapurinone deoxyribonucleoside 5-phosphate
-
additional information
-
functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers. The active-site configurations of ThyX proteins, present in many human pathogenic bacteria, and of human thymidylate synthase A (EC 2.1.1.45) are different.
-
additional information
Paramecium bursaria Chlorella virus-1
-
5-fluorouracil is not a potential inhibitor
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
FAD
-
increases activity
FMN
-
increases activity
NADH
-
required to reduce bound FAD
NADH
-
required to reduce bound FAD
NADPH
-
required to reduce bound FAD
NADPH
-
required to reduce bound FAD
NADPH
Q5UVJ4
0.1 mM NADPH saturates the enzymatic reaction
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.004
-
5,10-methylenetetrahydrofolate
-
-
0.02
-
5,10-methylenetetrahydrofolate
Paramecium bursaria Chlorella virus-1
-
-
0.35
-
5,10-methylenetetrahydrofolate
Q5UVJ4
in 50 mM Tris-HCl pH 8.0, 10 mM MgCl2, 2 mM NADPH, 0.5 mM FAD, at 22°C
0.00083
-
dUMP
-
mutant enzyme S84C
0.0012
-
dUMP
-
mutant enzyme R74K
0.0017
-
dUMP
-
mutant enzyme R74A
0.0037
-
dUMP
-
mutant enzyme S84A
0.0076
-
dUMP
-
wild-type enzyme
0.008
-
dUMP
-
mutant enzyme Y87F
0.012
-
dUMP
-
mutant enzyme S84Y
0.0122
-
dUMP
-
at 80 °C
0.015
-
dUMP
Paramecium bursaria Chlorella virus-1
-
-
0.0153
-
dUMP
Q5UVJ4
in 50 mM Tris-HCl pH 8.0, 10 mM MgCl2, 2 mM NADPH, 0.5 mM FAD, at 22°C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0038
-
dUMP
-
mutant enzyme Y87F
0.0072
-
dUMP
-
wild-type enzyme
0.0078
-
dUMP
-
mutant enzyme R74K
0.0097
-
dUMP
-
mutant enzyme S84Y
0.037
-
dUMP
-
mutant enzyme R74A
0.0384
-
dUMP
-
mutant enzyme S84A
0.14
-
dUMP
-
mutant enzyme S84C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00013
-
(heptanoyl[[(4R)-2-phenyl-3-(phenylcarbonyl)-1,3-thiazolidin-4-yl]methyl] amino)acetic acid
Q41156
-
0.0001
-
5-fluoro-2'-deoxyuridine 5'-monophosphate
-
inhibited both ThyA and ThyX
0.000057
-
ethyl (4R)-2-phenyl-3-([(1-(3-2,2,2-trifluoroacetamido)propyl)-1H-1,2,3-triazol-4-yl]carbonyl)-1,3-thiazolidine-4-carboxylate
Q41156
-
0.001
-
ethyl (4R)-2-phenyl-3-[[1-(2-thiophen-3-ylethyl)-1H-1,2,3-triazol-4-yl]carbonyl]-1,3-thiazolidine-4-carboxylate
Q41156
-
0.002
-
ethyl (4R)-3-([1-[2-(4-fluorophenyl)ethyl]-1H-1,2,3-triazol-4-yl]carbonyl)-2-phenyl-1,3-thiazolidine-4-carboxylate
Q41156
-
0.0035
-
ethyl (4R)-3-[[1-(7-hydroxyheptyl)-1H-1,2,3-triazol-4-yl]carbonyl]-2-phenyl-1,3-thiazolidine-4-carboxylate
Q41156
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.016
-
5,10-methylenetetrahydrofolate
Paramecium bursaria Chlorella virus-1
-
wild-type
0.048
-
5,10-methylenetetrahydrofolate
Paramecium bursaria Chlorella virus-1
-
R182A mutant
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.5
-
Q5UVJ4
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
10.5
Q5UVJ4
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
75
-
-, Q8U3C9
optimum RNA-binding activity
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-, Q8U3C9
no RNA-binding activity at 95°C
PDB
SCOP
CATH
ORGANISM
Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / LMG 3730 / NCIMB 10025)
Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / LMG 3730 / NCIMB 10025)
Helicobacter pylori (strain ATCC 700392 / 26695)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23800
-
-
SDS-PAGE
31000
-
-
SDS-PAGE
31500
-
-
calculated from DNA sequence
104000
-
-
gel filtration
111000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Paramecium bursaria Chlorella virus-1
-
x * 26000, SDS-PAGE
?
-
x * 27168.2, wild-type enzyme, MALDI-TOF
?
-, Q8U3C9
x * 29000, sequence analysis, x * 29000, SDS-PAGE
homotetramer
Paramecium bursaria Chlorella virus-1
-
crystallographic studies
homotetramer
-
crystallographic studies
homotetramer
Q5UVJ4
4 * 25000, SDS-PAGE; 4 * 25020, calculated from amino acid sequence; 4 * 25066, MALDI TOF mass spectrometry
homotetramer
-
4 * 25000, SDS-PAGE; 4 * 25020, calculated from amino acid sequence; 4 * 25066, MALDI TOF mass spectrometry
-
tetramer
-
4 * 31000, gel filtration, SDS-PAGE
tetramer
Q9WYT0
data from crystal structure
tetramer
-
predicted mass of a tetramer
tetramer
-
x-ray crystallography
tetramer
-
x-ray crystallography
-
tetramer
Thermotoga maritima TM0449
-
data from crystal structure
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
the ThyX sequence has an intein in itsThyX motif that does protein spicing and a group II intron, suggesting a hot spot for these self-splicing mobile elements
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hanging drop vapor diffusion method, using 0.2 M sodium chloride, 0.1 M MES, pH 6.0, and 20% (w/v) PEG2000 monomethyl ether
Q5UVJ4
in complex with FAD and dUMP
-
by the sitting-drop vapor diffusion method, in the presence of the cofactor FAD and the substrate analog BrdUMP, at 2.0 A resolution
-
I65M/L175M double mutant in the presence of FAD and BrdUMP, by the sitting-drop vapor-diffusion method, to 2.0 A resolution
-
crystal structure of the ThyX protein complexed to its FAD cofactor and solved by molecular replacement, to 2.3 A resolution, crystals belong to the P21212 space group with predicted two molecules per asymmetric unit and a solvent content of 51%
Paramecium bursaria Chlorella virus-1
-
crystal structure shows certain small structural differences in the active site when compared with either bacterial FDTS
Paramecium bursaria Chlorella virus-1
-
crystal structure shows no structural similarity with “classical” TS
-
mutants S88A and S88C, to 1.95 and 2.05 A resolution, respectively. Structure reveals minimlas changes in folding and active site conformation compared to wild-type. There is no covalent bond between the cysteine and dUMP in the crystal
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80°C, 10 mM Tris-HCl buffer, pH 7.2, 50 mM NaCl, 2 mM DTT, 100 mM FAD
-
-80°C, 50 mM HEPES buffer, pH 7.0, 10% glycerol
Paramecium bursaria Chlorella virus-1
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
from transformed E. coli
-
from transformed E. coli using His-tag
-
nickel chelating column chromatography, GSH-Sepharose column chromatography, and Superdex 200 gel filtration
Q5UVJ4
nickel affinity and ion-exchange chromatography
-
on Ni-NTA column
-
-
Paramecium bursaria Chlorella virus-1
-
by nickel chromatography and gel filtration, more than 95% pure
Paramecium bursaria Chlorella virus-1
-
to near homogeneity, by heat treatment at 85°C for 15 min, followed by Ni2+ column chromatography
-, Q8U3C9
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
complemetation of Escherichia coli thyA deletion mutant, transformants are able to grow in the absence of thymidine under oxygen limited conditions
-
complemetation of Haloferax volcanii thyA deletion mutant, transformants are able to grow in the absence of thymidine
-
complemetation of Escherichia coli, transformants are able to grow in the absence of thymidine
-
expressed in Escherichia coli M15 cells
Q5UVJ4
histidine-tagged Mycobacterium tuberculosis ThyX is overexpressed from BL21-DE3 pLysS Escherichia coli
-
I65M/L175M double mutant expressed in Escherichia coli BL21 (DE3) pLysS strain as C-terminal His6-tagged protein
-
into the pET24d vector, overexpressed in Escherichia coli chi2913 strain, plasmid containing the I65M/L175M double mutant expressed in Escherichia coli BL21 (DE3) pLysS strain
-
expression in Escherichia coli
Paramecium bursaria Chlorella virus-1
-
wild-type and mutant ThyX proteins expressed in either Escherichia coli DH5alpha (deltathyA) or BL21
Paramecium bursaria Chlorella virus-1
-
complemetation of Escherichia coli, transformants are unable to grow in the absence of thymidine
Q9UZ51
overexpression of the recombinant C-terminal His6-tagged protein in Escherichia coli strain BL21(DE3)
-, Q8U3C9
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
replacement of Escherichia coli thyA gene, EC 2.1.1.45, by thyX and expression under the native thyA promoter. In thymidine-deprived solid and liquid growth media, the mutant strain grows poorly compared with the wild-type strain and is impaired in DNA replication
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
H48Q
-
inactive mutant enzyme
H48Q/S84A
-
inactive mutant enzyme
H48Q/S84C
-
inactive mutant enzyme
R74A
-
the KM-value for dUMP is 5.1fold higher than the wild-type value, the turnover-number is 4.6fold lower than the wild-type value
R74K
-
the KM-value for dUMP is nearly identical to wild-type value, the turnover-number is 6.6fold lower than the wild-type value
S107A
-
no activity
S84A
-
the KM-value for dUMP is 5.3fold higher than the wild-type value, the turnover-number is 2.1fold lower than the wild-type value. Mutation abolishes thymidylate synthase activity in vivo
S84A/S85A
-
inactive mutant enzyme
S84C
-
mutation abolishes thymidylate synthase activity in vivo
S84Y
-
the KM-value for dUMP is 1.9fold higher than the wild-type value, the turnover-number is 1.6fold lower than the wild-type value
Y87F
-
the KM-value for dUMP is 1.8fold lower than the wild-type value, the turnover-number is nearly identical to the wild-type value
H69E
-
fails to complement the Escherichia coli chi2913 cells
I65M
-
no impaired enzyme activity, encodes proteins supporting the growth of Escherichia coli chi2913 strain
I65M/L175M
-
produces active ThyX enzyme
K165A
-
fails to complement the Escherichia coli chi2913 cells
R168A
-
fails to complement the Escherichia coli chi2913 cells
R95A
-
fails to complement the Escherichia coli chi2913 cells
R95D
-
fails to complement the Escherichia coli chi2913 cells
R95K
-
supports growth of Escherichia coli chi2913 cells
S105E
-
fails to complement the Escherichia coli chi2913 cells
Y108F
-
complemens the growth of Escherichia coli chi2913 cells
E190G
Paramecium bursaria Chlorella virus-1
-
no detectable activity
E190G
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, is capable of binding FAD at a wild-type level, but lacks detectable oxidation and deprotonation
H177K
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, 9.5% oxidation activity
H177Q
Paramecium bursaria Chlorella virus-1
-
confers thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, 31% oxidation activity
H53K
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, produces insoluble protein
H53Q
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, produces insoluble protein
H79K
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA
H79Q
Paramecium bursaria Chlorella virus-1
-
confers thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, 94% oxidation activity
R182A
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, does not copurify with oxidized FAD, but is able to oxidize NADPH in the presence of 0.4 mM FAD
R90A
Paramecium bursaria Chlorella virus-1
-
does not confer thymidine-independent growth to an Escherichia coli strain lacking thymidylate synthase ThyA, looses 44% of its oxidation activity and shows no measurable deprotonation activity
S88A
-
mutant retains activity. Residue S88 is not required for catalysis
S88C
-
mutant retains activity. Residue S88 is not required for catalysis
L175M
-
no impaired enzyme activity, encodes proteins supporting the growth of Escherichia coli chi2913 strain
additional information
-
analysis of 67 site-directed mutants and identification of the extended motif Y44X(24)H69X(25)R95HRX(87)S105XRYX(90)R199 of amino acids essential to enzyme activity. Residue H69 is the catalytic residue, S105 the nucleophile
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
Clostridium botulinum, Clostridium difficile
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promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low crossreactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low crossreactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
drug development
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unexpected observation that NADP+ competes with both FAD and substrate for the binding site in ThyX and displaces both molecules from the active site, opens avenues for the design of tight-binding inhibitors of ThyX enzymes from a variety of organisms
medicine
-
specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human
medicine
-
promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
Q9WYT0
the unique mechanism of FDTS makes it an attractive target for antibiotic drug development
medicine
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antibiotic target
medicine
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promising medical target, thyX is present in a number of pathogenic bacteria but absent in human; specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45
medicine
-
thymidylate synthase as a target for antitubercular drugs
additional information
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complements the Escherichia coli chi2913 strain that lacks its conventional TS activity, residues Lys165 and Arg168 play critical roles in ThyX activity, possibly by governing access to the carbon atom to be methylated of a totally buried substrate dUMP
additional information
Paramecium bursaria Chlorella virus-1
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residues His53, Glu190, Arg90, and Arg182 are essential for TS activity
additional information
-, Q8U3C9
autoregulates its own translation, RNA stem-loop structure acts as an inhibitory regulator of translation by preventing the binding of its Shine-Dalgarno-like sequence by positioning it in the stem region, addition of Thy1 into the in vitro translation system also inhibits translation