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Information on EC 4.1.3.32 - 2,3-Dimethylmalate lyase
for references in articles please use BRENDA:EC4.1.3.32
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 4.1.3.32
-
nicotinic
- barkeri
- clostridium
- phosphoenolpyruvate
- propionate
- icl
- niger
- tuberculosis
- oxalate
-
gem-diol
- isocitrate
-
racemic
- dimethylmaleate
showSynonyms
2,3-dimethylmalate lyase, (2r,3s)-dimethylmalate lyase, an07g08390, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(2R,3S)-dimethylmalate lyase
DMML
Lyase, 2,3-dimethylmalate
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(2R,3S)-2,3-dimethylmalate = propanoate + pyruvate
cleavage reaction on (2R,3S)-2,3-dimethylmalate lyase proceeds with inversion of configuration at C-3 of the substrate which becomes C-2 of propanoate
-
(2R,3S)-2,3-dimethylmalate = propanoate + pyruvate
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
nicotinate degradation III
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SYSTEMATIC NAME
IUBMB Comments
(2R,3S)-2,3-dimethylmalate pyruvate-lyase (propanoate-forming)
-
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CAS REGISTRY NUMBER
COMMENTARY
73562-28-4
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2R,3S)-2,3-dimethylmalate
propanoate + pyruvate
Substrates: -
Products: -
Products: -
?
(2R,3S)-2,3-dimethylmalate
propanoate + pyruvate
-
Substrates: -
Products: -
Products: -
?
(2R,3S)-2,3-dimethylmalate
propanoate + pyruvate
-
Substrates: -
Products: -
Products: -
?
(2R,3S)-dimethylmalate
propanoate + pyruvate
Substrates: -
Products: -
Products: -
?
(2R,3S)-dimethylmalate
propanoate + pyruvate
-
Substrates: -
Products: -
Products: -
?
2,3-Dimethylmalate
Propanoate + pyruvate
-
Substrates: -
Products: -
Products: -
?
2,3-Dimethylmalate
Propanoate + pyruvate
-
Substrates: (2R,3S)-2,3-dimethylmalate
Products: -
Products: -
?
additional information
?
-
Substrates: (2R,3S)-isocitrate, (R)-malate, (S)-malate, (2S)-methylmalate, (3S)-isopropylmalate, 3-butylmalate, phosphonopyruvate, carboxyphenolpyruvate, 3,3-difluoroxaloacetate, oxalate are no substrates
Products: -
Products: -
?
additional information
?
-
-
Substrates: (2R,3S)-isocitrate, (R)-malate, (S)-malate, (2S)-methylmalate, (3S)-isopropylmalate, 3-butylmalate, phosphonopyruvate, carboxyphenolpyruvate, 3,3-difluoroxaloacetate, oxalate are no substrates
Products: -
Products: -
?
additional information
?
-
Substrates: DMML also possesses significant oxaloacetate acetyl hydrolase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: DMML also possesses significant oxaloacetate acetyl hydrolase activity
Products: -
Products: -
?
additional information
?
-
Substrates: (2R,3S)-isocitrate, (R)-malate, (S)-malated, (2S)-methylmalate, (3S)-isopropylmalate, 3-butylmalate, phosphonopyruvate, carboxyphosphoenolpyruvate, 3,3-difluoroxaloacetate, and oxalate are no substrates
Products: -
Products: -
?
additional information
?
-
-
Substrates: (2R,3S)-isocitrate, (R)-malate, (S)-malated, (2S)-methylmalate, (3S)-isopropylmalate, 3-butylmalate, phosphonopyruvate, carboxyphosphoenolpyruvate, 3,3-difluoroxaloacetate, and oxalate are no substrates
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2R,3S)-2,3-dimethylmalate
propanoate + pyruvate
Substrates: -
Products: -
Products: -
?
(2R,3S)-2,3-dimethylmalate
propanoate + pyruvate
-
Substrates: -
Products: -
Products: -
?
(2R,3S)-2,3-dimethylmalate
propanoate + pyruvate
-
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
Mg2+
-
influence of Mg2+ on the equilibrium, inhibition at high concentration
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
(2R,3S)-isocitrate, (R)-malate, (S)-malate, and carboxyphosphoenolpyruvate are not inhibitors
-
additional information
-
(2R,3S)-isocitrate, (R)-malate, (S)-malate, and carboxyphosphoenolpyruvate are not inhibitors
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.17
(2R)-ethyl-(3S)-methylmalate
wild type enzyme, at pH 7.5 and 25°C
1.17
(2R)-ethyl-(3S)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
12
(2R)-ethylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
2.2
(2R)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
2.7
(2R)-propyl-(3S)-methylmalate
wild type enzyme, at pH 7.5 and 25°C
2.7
(2R)-propyl-(3S)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
12
(2R,3S)-2-methylisocitrate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.036
(2R,3S)-dimethylmalate
mutant enzyme C124A, at pH 7.5 and 25°C
0.036
(2R,3S)-dimethylmalate
mutant enzyme C124A, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.22
(2R,3S)-dimethylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
3.6
(2R,3S)-dimethylmalate
mutant enzyme C124S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
4.1
(2R,3S)-dimethylmalate
mutant enzyme P240T, in 50 mM K+-HEPES (pH 7.5 and 25°C)
5.9
(2R,3S)-dimethylmalate
mutant enzyme P240S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
6
(2R,3S)-dimethylmalate
mutant enzyme D59S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
7.4
(2R,3S)-dimethylmalate
mutant enzyme D59A, in 50 mM K+-HEPES (pH 7.5 and 25°C)
12
(2S,3R)-2-methylisocitrate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
19.2
(2R,3S)-2,3-dimethylmalate
-
pH and temperature not specified in the publication
0.00001
3,3-difluorooxaloacetate
-
kcat less than 0.00001 sec-1, pH and temperature not specified in the publication
63
(2R)-ethyl-(3S)-methylmalate
wild type enzyme, at pH 7.5 and 25°C
63
(2R)-ethyl-(3S)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
4.4
(2R)-ethylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
2.6
(2R)-methylmalate
-
pH and temperature not specified in the publication
2.64
(2R)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.79
(2R)-propyl-(3S)-methylmalate
wild type enzyme, at pH 7.5 and 25°C
0.79
(2R)-propyl-(3S)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.13
(2R,3S)-2-methylisocitrate
wild type enzyme, at pH 7.5 and 25°C
0.13
(2R,3S)-2-methylisocitrate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.00001
(2R,3S)-dimethylmalate
mutant Y44F, smaller than 0.00001 s-1
0.00001
(2R,3S)-dimethylmalate
mutant enzyme Y44F, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.000121
(2R,3S)-dimethylmalate
mutant enzyme C124S, at pH 7.5 and 25°C
0.000121
(2R,3S)-dimethylmalate
mutant enzyme C124S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.00014
(2R,3S)-dimethylmalate
mutant enzyme D59S, at pH 7.5 and 25°C
0.00014
(2R,3S)-dimethylmalate
mutant enzyme D59S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.000178
(2R,3S)-dimethylmalate
mutant enzyme C124A, at pH 7.5 and 25°C
0.000178
(2R,3S)-dimethylmalate
mutant enzyme C124A, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.000427
(2R,3S)-dimethylmalate
mutant enzyme D59A, at pH 7.5 and 25°C
0.000427
(2R,3S)-dimethylmalate
mutant enzyme D59A, in 50 mM K+-HEPES (pH 7.5 and 25°C)
2.8
(2R,3S)-dimethylmalate
mutant enzyme P240T, in 50 mM K+-HEPES (pH 7.5 and 25°C)
11.7
(2R,3S)-dimethylmalate
mutant enzyme P240S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
19.2
(2R,3S)-dimethylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.13
(2S,3R)-2-methylisocitrate
wild type enzyme, at pH 7.5 and 25°C
0.13
(2S,3R)-2-methylisocitrate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.00001
(S)-malate
-
kcat less than 0.00001 sec-1, pH and temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
50
(2R)-ethyl-(3S)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.1
(2R)-ethylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
1
(2R)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.3
(2R)-propyl-(3S)-methylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.01
(2R,3S)-2-methylisocitrate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.01
(2S,3R)-2-methylisocitrate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
0.005
(2R,3S)-dimethylmalate
mutant enzyme C124A, in 50 mM K+-HEPES (pH 7.5 and 25°C)
20
(2R,3S)-dimethylmalate
mutant enzyme D59S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
30
(2R,3S)-dimethylmalate
mutant enzyme C124S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
60
(2R,3S)-dimethylmalate
mutant enzyme D59A, in 50 mM K+-HEPES (pH 7.5 and 25°C)
90
(2R,3S)-dimethylmalate
wild type enzyme, in 50 mM K+-HEPES (pH 7.5 and 25°C)
700000
(2R,3S)-dimethylmalate
mutant enzyme P240T, in 50 mM K+-HEPES (pH 7.5 and 25°C)
2000000
(2R,3S)-dimethylmalate
mutant enzyme P240S, in 50 mM K+-HEPES (pH 7.5 and 25°C)
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
31990
32000
32120
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
DMML in complex with Mg2+ and in complex with Mg2+ and 3,3-difluorooxalacetate, hanging drop vapor diffusion method, using 0.2 M potassium thiocyanate, 0.1 M bis-Tris propane (pH 7.5), and 20k polyethylene glycol 3350, or using 14k polyethylene glycol 6000 and 0.1 M MES (pH 6.5)
the crystal structure of DMML in complex with Mg2+ and in complex with Mg2+ and a substrate analog, the gem-diol of 3,3-difluoro-oxaloacetate, is determined
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C124A
C124S
D59A
D59S
P240S
P240T
Y44F
C124A
site-directed mutant for testing the contributions made by key active-site residues
C124A
the mutant shows decreased kcat compared to the wild type enzyme
C124S
site-directed mutant for testing the contributions made by key active-site residues
C124S
the mutant shows decreased kcat compared to the wild type enzyme
D59A
site-directed mutant for testing the contributions made by key active-site residues
D59A
the mutant shows decreased kcat compared to the wild type enzyme
D59S
site-directed mutant for testing the contributions made by key active-site residues
D59S
the mutant shows decreased kcat compared to the wild type enzyme
P240S
site-directed mutant for testing the contributions made by key active-site residues
P240S
the mutant shows decreased kcat compared to the wild type enzyme
P240T
site-directed mutant for testing the contributions made by key active-site residues
P240T
the mutant shows decreased kcat compared to the wild type enzyme
Y44F
site-directed mutant for testing the contributions made by key active-site residues
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
(NH4)2SO4 precipitation, Source Phe column chromatography, and Source 15Q FPLC column chromatography
-
Q-Sepharose column chromatography, ammonium sulfate precipitation, butyl Sepharose column chromatography, and phenyl Sepharose column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
into the vector pGEM-T Easy and subsequently into pET3c for expression in Escherichia coli BL21DE3 cells
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pirzer, P.; Lill, U.; Eggerer, H.
Nicotinic acid metabolism. 2,3-Dimethylmalate lyase
Hoppe-Seyler's Z. Physiol. Chem.
360
1693-1702
1979
Eubacterium barkeri
brenda
Lill, U.; Pirzer, P.; Kukla, D.; Huber, R.; Eggerer, H.
Nicotinic acid metabolism. Enzymic preparation and absolute configuration of the substrate for 2,3-dimethylmalate lyase
Hoppe-Seyler's Z. Physiol. Chem.
361
875-884
1980
Eubacterium barkeri
brenda
Lhlein, G.; Eggerer, H.
Nicotinic acid metabolism. Stereochemical course of the (2R,3S)-2,3-dimethylmalate lyase reaction
Hoppe-Seyler's Z. Physiol. Chem.
363
1103-1109
1982
Eubacterium barkeri
brenda
Eggerer, H.
Completion of the degradation scheme for nicotinic acid by Clostridium barkeri
Curr. Top. Cell. Regul.
26
411-418
1985
Eubacterium barkeri
brenda
Alhapel, A.; Darley, D.J.; Wagener, N.; Eckel, E.; Elsner, N.; Pierik, A.J.
Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri
Proc. Natl. Acad. Sci. USA
103
12341-12346
2006
Eubacterium barkeri
brenda
Narayanan, B.; Niu, W.; Joosten, H.J.; Li, Z.; Kuipers, R.K.; Schaap, P.J.; Dunaway-Mariano, D.; Herzberg, O.
Structure and function of 2,3-dimethylmalate lyase, a PEP mutase/isocitrate lyase superfamily member
J. Mol. Biol.
386
486-503
2009
Aspergillus niger (Q2L887), Aspergillus niger
brenda
Chotpatiwetchkul, W.; Jongkon, N.; Hannongbua, S.; Gleeson, M.P.
QM/MM investigation of the reaction rates of substrates of 2,3-dimethylmalate lyase A catabolic protein isolated from Aspergillus niger
J. Mol. Graph. Model.
68
29-38
2016
Aspergillus niger
brenda
Jongkon, N.; Chotpatiwetchkul, W.; Gleeson, M.P.
Probing the catalytic mechanism involved in the isocitrate lyase superfamily hybrid quantum mechanical/molecular mechanical calculations on 2,3-dimethylmalate lyase
J. Phys. Chem. B
119
11473-11484
2015
Mycobacterium tuberculosis
brenda
EXTERNAL LINKS (specific for EC-Number 4.1.3.32)
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