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2.1.1.45: thymidylate synthase

This is an abbreviated version!
For detailed information about thymidylate synthase, go to the full flat file.

Word Map on EC 2.1.1.45

Reaction

5,10-methylenetetrahydrofolate
+
dUMP
=
dihydrofolate
+
dTMP

Synonyms

BgDHFR-TS, bifunctional TS-DHFR, DFR-TS, DHFR-TS, DHFR–TS, dihydrofolate reductase-thymidylate synthase, dTMP synthase, HTS, human TS, LBRM_06_0830, methylenetetrahydrofolate:dUMP C-methyltransferase, More, Thy1, ThyA, thymidylate synthase, thymidylate synthase A, thymidylate synthase-dihydrofolate reductase, thymidylate synthetase, ThyX, TMP synthetase, TMPS, TS, TS-DHFR, TSase, TYMS, Y110A7A.4

ECTree

     2 Transferases
         2.1 Transferring one-carbon groups
             2.1.1 Methyltransferases
                2.1.1.45 thymidylate synthase

Engineering

Engineering on EC 2.1.1.45 - thymidylate synthase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R166K
residue R166 is involved in both C-H bond activations
A17T/D116A/D254E
-
the mutant shows decreased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
A191K
D254N
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
E30W
-
the mutant shows 100times lower specific activity with respect to the wild type enzyme and is resistant to 5-fluoro-2'-deoxyuridine-5'-monophosphate (6fold higher inhibition constant than the wild type enzyme)
F59A
crucial dimer interface residue
G52S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
K47A
mutation at dimer interface
L198A
crucial dimer interface residue
L198P
the mutant enzyme displays a kcat value of 2fold lower than wild type
M190E
the mutant enzyme displays a kcat value of 5.9fold lower than wild type
M190K
R163K
T51S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T51S/G52S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T51S/K82Q/K99E/N171S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T53S/Y258F
-
the mutant shows sensitivity towards 5-fluorodeoxyuridine similar to the wild type enzyme
V3A
-
the mutant enzyme has an intracellular half-life of approximately 6 h after treatment with cycloheximide
V3F
-
the mutant enzyme has an intracellular half-life of approximately 3.5 h after treatment with cycloheximide
V3L
-
the mutant enzyme has an intracellular half-life of approximately 2.5 h after treatment with cycloheximide
V3T
-
the mutant enzyme has an intracellular half-life of approximately 24 h after treatment with cycloheximide
V3Y
-
the mutant enzyme has an intracellular half-life of approximately 2.5 h after treatment with cycloheximide
Y202A
crucial dimer interface residue, activity similar to wild-type
Y258F
-
the mutant shows decreased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T155C/E188C/C244T
-
formation of 2 disulfide crosslinks across the subunit interface results in dramatic stabilization of the overall structure of the protein, retention of secondary structure at temperatures as high as 90°C, engineering of an intersubunit crosslink yields a fully active enzyme
G5L/S6A
-
the mutant has a relatively short half-life of about 1-2 h
P2A
-
the mutant enzyme is quite stable relative to wild type enzyme with half-life of more than 36-48 h
P2D
-
the mutant enzyme is quite stable relative to wild type enzyme with half-life of more than 36-48 h
P2G
-
the mutant is unstable relative to wild type enzyme having half-life of 6-8 h similar to wild type
P2R
-
the mutant enzyme is quite stable relative to wild type enzyme with half-life of more than 36-48 h
P2V
-
the mutant is unstable relative to wild type enzyme having half-life of 1-2 h with half-life of more than 36-48 h
P2W
-
the mutant enzyme is quite stable relative to wild type enzyme with half-life of more than 36-48 h
P2Y
-
the mutant enzyme is quite stable relative to wild type enzyme with half-life of more than 36-48 h
C490A
-
inactive
R470D
-
inactive
C506A
-
inactive
C506D
-
inactive
C506F
-
inactive
C506P
-
inactive
C506Y
-
inactive
R486D
-
inactive
R486L
-
inactive
R486Y
-
inactive
S290G
site-directed mutagenesis, the mutant shows 10fold reduced activity compared to the wild-type enzyme
additional information