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Information on EC 2.1.2.11 - 3-methyl-2-oxobutanoate hydroxymethyltransferase and Organism(s) Escherichia coli and UniProt Accession P31057
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2.1.2.11 3-methyl-2-oxobutanoate hydroxymethyltransferaseSpecify your search results
Word Map
- 2.1.2.11
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pantothen
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auxotrophs
-
aldol
- l-valine
- beta-alanine
-
pane
-
betaalpha8
- 2-oxoacids
- pharmacology
- alpha-ketobutyrate
-
decameric
- 4'-phosphopantetheine
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
ketopantoate hydroxymethyltransferase, kphmt, 3-methyl-2-oxobutanoate hydroxymethyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5,10-methylene tetrahydrofolate:alpha-ketoisovalerate hydroxymethyltransferase
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-
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alpha-ketoisovalerate hydroxymethyltransferase
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-
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dehydropantoate hydroxymethyltransferase
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-
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hydroxymethyltransferase, ketopantoate
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-
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ketopantoate hydroxymethyltransferase
KHMT
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KPHMT
oxopantoate hydroxymethyltransferase
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-
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ketopantoate hydroxymethyltransferase
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-
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KPHMT
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O = tetrahydrofolate + 2-dehydropantoate
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O = tetrahydrofolate + 2-dehydropantoate
stereochemistry
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5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O = tetrahydrofolate + 2-dehydropantoate
class II aldolase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydroxymethyl group transfer
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-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -
SYSTEMATIC NAME
IUBMB Comments
5,10-methylenetetrahydrofolate:3-methyl-2-oxobutanoate hydroxymethyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
56093-17-5
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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
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O
tetrahydrofolate + 2-dehydropantoate
-
-
-
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxopentanoate
?
-
-
-
-
?
tetrahydropteroyldiglutamate + 2-dehydropantoate
5,10-methylenetetrahydropteroyldiglutamate + 3-methyl-2-oxobutanoate + H2O
-
-
-
-
r
tetrahydropteroylheptaglutamate + 2-dehydropantoate
5,10-methylenetetrahydropteroylheptaglutamate + 3-methyl-2-oxobutanoate + H2O
-
-
-
-
r
tetrahydropteroylhexaglutamate + 2-dehydropantoate
5,10-methylenetetrahydropteroylhexaglutamate + 3-methyl-2-oxobutanoate + H2O
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-
-
-
r
tetrahydropteroylpentaglutamate + 2-dehydropantoate
5,10-methylenetetrahydropteroylpentaglutamate + 3-methyl-2-oxobutanoate + H2O
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-
-
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r
tetrahydropteroyltetraglutamate + 2-dehydropantoate
5,10-methylenetetrahydropteroyltetraglutamate + 3-methyl-2-oxobutanoate + H2O
-
-
-
-
r
tetrahydropteroyltriglutamate + 2-dehydropantoate
5,10-methylenetetrahydropteroyltriglutamate + 3-methyl-2-oxobutanoate + H2O
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-
-
-
r
additional information
?
-
-
no substrates: pyruvate, isovalerate, D- and L-valine, 3-methyl-2-butanone
-
-
?
5,10-methylenetetrahydrofolate + 2-oxobutyrate
?
-
also a good substrate
-
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
-
-
r
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
-
formation of ketopantoate, syn. 2-keto-3,3-dimethyl-4-hydroxybutyrate, tetrahydrofolate-dependent enzyme
r
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
-
synthesis of ketopantoate, the following components can replace tetrahydrofolate: tetrahydropteroylmono-, di-, tri-, tetra-, penta-, hexa-, and heptaglutamate, absolute requirement for tetrahydrofolate, only the L-isomer is active
r
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
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forms 2-oxopantoate, syn. 3-hydroxymethyl-3-methyl-2-oxobutanoic acid, from 2-oxoisovalerate with retention of configuration at C-3
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
condensation of alpha-ketoisovalerate with the C-1 donor takes place stereospecifically at C-3 and proceeds in a retention mode at C-3, 5,10-methylenetetrahydrofolate-dependent enzyme
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r
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
specificity for alpha-ketoisovalerate is less rigid than for tetrahydrofolate
synthesis of ketopantoate, the following components can replace tetrahydrofolate: tetrahydropteroylmono-, di-, tri-, tetra-, penta-, hexa-, and heptaglutamate, absolute requirement for tetrahydrofolate, only the L-isomer is active
r
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
inversion of the configuration at C-3 of 2-ketoisovalerate
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
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?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
enzyme is responsible for catalysis of ketopantoate formation in vivo
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
catalytic activity is regulated by the products of the reaction path of which it is one component
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
biosynthesis of coenzyme A
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
biosynthesis of coenzyme A
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first step in pantoate biosynthesis
-
?
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
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O
tetrahydrofolate + 2-dehydropantoate
-
-
-
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
-
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first committed step in pantothenate biosynthesis
enzyme is responsible for catalysis of ketopantoate formation in vivo
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
catalytic activity is regulated by the products of the reaction path of which it is one component
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
biosynthesis of coenzyme A
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
biosynthesis of coenzyme A
-
?
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate
tetrahydrofolate + 2-dehydropantoate
-
first step in pantoate biosynthesis
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no requirement of pyridoxal 5-phosphate as cofactor
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5,10-methylenetetrahydrofolate
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5,10-methylenetetrahydrofolate-dependent enzyme
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Mg2+
Mn2+
Zn2+
Mg2+
-
activates and is required for activity, 0.1 mM Mg2+ is most active, Mn2+, Ni2+, Co2+ and Zn2+ are progressively less active, restores activity after dialysis
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
not inactivated by borohydride reduction in the presence of excess substrates
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
low Km-values for its substrates
-
5.9
formaldehyde
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methylenetetrahydrofolate: formaldehyde + tetrahydrofolate
0.18
tetrahydrofolate
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forward and reverse reaction, methylenetetrahydrofolate: formaldehyde + tetrahydrofolate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
enzyme overexpression leads to accumulation of the likely folate cleavage product 6-hydroxymethylpterin and other pterins in cells and medium, and to a 46% increase in total folate content
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28179
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6 * 28179, calculated from the amino acid sequence and electrospray mass spectrometry, 6 * 29000, recombinant enzyme expressed in Escherichia coli Hfr3000 YA139/pCEJ01, SDS-PAGE
29000
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6 * 28179, calculated from the amino acid sequence and electrospray mass spectrometry, 6 * 29000, recombinant enzyme expressed in Escherichia coli Hfr3000 YA139/pCEJ01, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
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6 * 28179, calculated from the amino acid sequence and electrospray mass spectrometry, 6 * 29000, recombinant enzyme expressed in Escherichia coli Hfr3000 YA139/pCEJ01, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily
hanging drop vapor diffusion, crystal structure at 1.9 A resolution in complex with its product ketopantoate, the enzyme adopts the (betaalpha)8 barrel fold and the active site contains a ketopantoate bidentately coordiated to Mg2+
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
-
treatment at 55°C largely destroys enzyme in crude extract, partially purified enzyme is more heat-stabile
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate fractionation inactivates, resistant to urea denaturation
-
not inactivated by borohydride reduction in the presence of excess substrates
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 100 mM potassium phosphate, pH 6.8, 1 mM EDTA, 0.5 mM dithiothreitol, 6 months, almost no loss of activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
19.3fold purification of recombinant enzyme 50fold overexpressed in E. coli panB mutant Hfr3000 YA139/pCEJ01
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
panB gene encoding enzyme is cloned, sequenced and 50fold overexpressed in Escherichia coli panB mutant Hfr3000 YA139 containing plasmid pCEJ01, gene is 792 bp long and encodes a protein of 264 amino acids, gene is likely to be cotranscribed with at least one other gene, panB, panC and panD genes are closely clustered at 3.1 min of the Escherichia coli K12 genetic map
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Teller, J.H.; Powers, S.G.; Snell, E.E.
Ketopantoate hydroxymethyltransferase. I. Purification and role in pantothenate biosynthesis
J. Biol. Chem.
251
3780-3785
1976
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
Powers, S.G.; Snell, E.E.
Ketopantoate hydroxymethyltransferase. II. Physical, catalytic, and regulatory properties
J. Biol. Chem.
251
3786-3793
1976
Escherichia coli
Powers, S.G.; Snell, E.E.
Purification and properties of ketopantoate hydroxymethyltransferase
Methods Enzymol.
62
204-209
1979
Escherichia coli
Wightman, R.H.
Stereochemistry of 2-oxopantoate formation by oxopantoate hydroxymethyltransferase
J. Chem. Soc. Chem. Commun.
1979
818-819
1979
Escherichia coli
-
Aberhart, D.J.
Stereochemistry of pantoate biosynthesis from 2-ketoisovalerate
J. Am. Chem. Soc.
101
1354-1355
1979
Escherichia coli
-
Aberhart, D.J.; Russell, D.J.
Steric course of ketopantoate hydroxymethyltransferase in E. coli
J. Am. Chem. Soc.
106
4902-4906
1984
Escherichia coli
-
Jones, C.E.; Brook, J.M.; Buck, D.; Abell, C.; Smith, A.G.
Cloning and sequencing of the Escherichia coli panB gene, which encodes ketopantoate hydroxymethyltransferase, and overexpression of the enzyme
J. Bacteriol.
175
2125-2130
1993
Escherichia coli
Schmitzberger, F.; Smith, A.G.; Abell, C.; Blundell, T.L.
Comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily
J. Bacteriol.
185
4163-4171
2003
Escherichia coli (P31057), Escherichia coli
von Delft, F.; Inoue, T.; Saldanha, S.A.; Ottenhof, H.H.; Schmitzberger, F.; Birch, L.M.; Dhanaraj, V.; Witty, M.; Smith, A.G.; Blundell, T.L.; Abell, C.
Structure of E. coli ketopantoate hydroxymethyl transferase complexed with ketopantoate and Mg2+, solved by locating 160 selenomethionine sites
Structure
11
985-996
2003
Escherichia coli
Thiaville, J.J.; Frelin, O.; Garcia-Salinas, C.; Harrison, K.; Hasnain, G.; Horenstein, N.A.; Diaz de la Garza, R.I.; Henry, C.S.; Hanson, A.D.; de Crecy-Lagard, V.
Experimental and metabolic modeling evidence for a folate-cleaving side-activity of ketopantoate hydroxymethyltransferase (PanB)
Front. Microbiol.
7
431
2016
Escherichia coli, Escherichia coli W3110
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