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Information on EC 2.7.1.49 - hydroxymethylpyrimidine kinase and Organism(s) Escherichia coli and UniProt Accession P76422
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2.7.1.49 hydroxymethylpyrimidine kinaseIUBMB Comments
CTP, UTP and GTP can act as donors.
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Word Map
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
hmp kinase, hmppk, hmp-p kinase, sthmppk, tthmppk, hydroxymethylpyrimidine kinase, 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase, 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate kinase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
hydroxymethylpyrimidine kinase (phosphorylating)
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP:4-amino-5-hydroxymethyl-2-methylpyrimidine 5-phosphotransferase
CTP, UTP and GTP can act as donors.
CAS REGISTRY NUMBER
COMMENTARY
9026-55-5
-
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
ATP + 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine
ADP + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine
ATP + 4-amino-5-hydroxymethyl-2-methylpyrimidine
ADP + 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine
-
-
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
ATP + 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine
ADP + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine
-
-
-
?
ATP + 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine
ADP + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine
reaction of EC 2.7.4.7
-
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
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-
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
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-
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
-
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
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involved in thiamine biosynthetic pathway, first steps
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
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involved in thiamine biosynthetic pathway, first steps
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
involved in thiamine biosynthetic pathway, first steps
-
?
additional information
?
-
the enzyme performs double phosphorylation on 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP)
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-
-
additional information
?
-
-
bifunctional hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase
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-
?
additional information
?
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bifunctional hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase
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-
?
additional information
?
-
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enzyme is probably different from previously isolated HMP kinase, because the subunit molecular masses are significantly different
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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
ATP + 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine
ADP + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine
-
-
-
?
ATP + 4-amino-5-hydroxymethyl-2-methylpyrimidine
ADP + 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine
-
-
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
-
involved in thiamine biosynthetic pathway, first steps
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
-
involved in thiamine biosynthetic pathway, first steps
-
?
ATP + 2-methyl-4-amino-5-hydroxymethylpyrimidine
ADP + 2-methyl-4-amino-5-phosphomethylpyrimidine
involved in thiamine biosynthetic pathway, first steps
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxine
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inhibits competitively the phosphorylation of 2-methyl-4-amino-5-hydroxymethylpyrimidine
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00104
4-Amino-5-hydroxymethyl-2-methylpyrimidine
pH 7.5, temperature not specified in the publication, recombinant enzyme ThiD
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.285
4-Amino-5-hydroxymethyl-2-methylpyrimidine
pH 7.5, temperature not specified in the publication, recombinant enzyme ThiD
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
274.04
4-Amino-5-hydroxymethyl-2-methylpyrimidine
pH 7.5, temperature not specified in the publication, recombinant enzyme ThiD
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 6
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about half-maximal activity at pH 5.0 and pH 6.0, pyridoxine as substrate
5.5 - 6.5
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about half-maximal activity at pH 5.5 and pH 6.5, 2-methyl-4-amino-5-hydroxymethylpyrimidine as substrate
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
ThiD is a member of the ribokinase family, but differs from other members in catalyzing two consecutive phosphorylations. The other members of the family catalyze only the phosphorylation of a hydroxymethyl group to give a monophosphate, i.e. the equivalent of the HMP kinase reaction. The HMP kinase activity of ThiD is hence presumably ancestral and the HMP-P kinase activity is an evolutionary novelty
metabolism
the enzyme takes part in the bacterial thiamin biosynthesis and salvage pathways, overview
physiological function
the bifunctional canonical kinase (ThiD) that converts the thiamin biosynthesis intermediate hydroxymethylpyrimidine (HMP) monophosphate into the diphosphate (EC 2.7.4.7) can also very efficiently convert free HMP into the monophosphate (EC 2.7.1.49) in prokaryotes, plants, and fungi. This HMP kinase activity enables salvage of HMP, but it is not substrate-specific and so allows toxic HMP analogues and damage products to infiltrate the thiamin biosynthesis pathway
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
gel filtration indicates the enzyme is tetrameric in the native state
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
tetramer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
construction of a thiD knockout mutant strain, complementation of the Escherichia coli DELTA thiD knockout mutant is possible by heterologous expression of gene ThiD2, ThiD2 proteins catalyze phosphorylation of HMP monophosphate, but not of HMP or its toxic analogues and damage products such as bacimethrin and 5-(hydroxymethyl)-2-methylpyrimidin-4-ol. As strictly monofunctional HMP monophosphate kinases (EC 2.7.4.7), ThiD2 proteins eliminate a potentially fatal vulnerability of canonical ThiD, at the cost of the ability to reclaim HMP formed by thiamin turnover
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Escherichia coli BL21(DE3) (pLysS) transformed with pTRD63 carrying ORF2, single gene thiD/J encodes 2 distinct enzyme activities, HMP kinase and HMP-P kinase, functional complemetation of Escherichia coli NI500, overexpression of ThiD
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
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useful reagent for the preparation of intermediates on the thiamin biosynthetic pathway
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mizote, T.; Nakayama, H.
Purification and properties of hydroxymethylpyrimidine kinase from Escherichia coli
Biochim. Biophys. Acta
991
109-113
1989
Escherichia coli
Reddick, J.J.; Kinsland, C.; Nicewonger, R.; Christian, T.; Downs, D.M.; Winkler, M.E.; Begley, T.P.
Overexpression, purification and characterization of two pyrimidine kinases involved in the biosynthesis of thiamin: 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase and 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase
Tetrahedron
54
15983-15991
1998
Escherichia coli
-
Mizote, T.; Tsuda, M.; Smith, D.D.; Nakayama, H.; Nakazawa, T.
Cloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase
Microbiology
145
495-501
1999
Escherichia coli, Escherichia coli (P76422), Escherichia coli BL21(DE3) (pLysS)
Thamm, A.M.; Li, G.; Taja-Moreno, M.; Gerdes, S.Y.; de Crecy-Lagard, V.; Bruner, S.D.; Hanson, A.D.
A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin biosynthesis
Biochem. J.
474
2887-2895
2017
Escherichia coli (P76422), Escherichia coli BW25113 (P76422)
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