Information on EC 4.2.1.18 - methylglutaconyl-CoA hydratase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
4.2.1.18
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RECOMMENDED NAME
GeneOntology No.
methylglutaconyl-CoA hydratase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(S)-3-hydroxy-3-methylglutaryl-CoA = trans-3-methylglutaconyl-CoA + H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
ferrichrome A biosynthesis
-
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L-leucine degradation I
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Metabolic pathways
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Valine, leucine and isoleucine degradation
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leucine metabolism
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SYSTEMATIC NAME
IUBMB Comments
(S)-3-hydroxy-3-methylglutaryl-CoA hydro-lyase (trans-3-methylglutaconyl-CoA-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9024-24-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
DSMZ 11652, strain IVS-B, formerly classified as Mycobacterium IVS-B
SwissProt
Manually annotated by BRENDA team
DSMZ 11652, strain IVS-B, formerly classified as Mycobacterium IVS-B
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
PA2011
-
-
Manually annotated by BRENDA team
PA2011
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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enzyme deficiency, due to homozygous deletion of exons 1-3 within the AUH gene, leads to 3-methylglutaconic aciduria type I with phenotypic heterogeneity, e.g. learning disability, attention deficit-hyperactivity and early onset subclinical leukoencephalopathy or severe expressive speech delay and delay in speech sound development with normal cognitive functions, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(E)-3-methylglutaconyl-1-CoA
?
show the reaction diagram
different co-substrates tested
-
-
?
(E)-glutaconyl-CoA
?
show the reaction diagram
(R,S)-3-hydroxy-3-methylglutaryl-CoA
?
show the reaction diagram
different co-substrates tested
-
-
?
(S)-3-Hydroxy-3-methylglutaryl-CoA
?
show the reaction diagram
(S)-3-hydroxy-3-methylglutaryl-CoA
trans-3-methylglutaconyl-CoA + H2O
show the reaction diagram
(S)-3-hydroxyglutaryl-CoA
?
show the reaction diagram
3-hydroxybutyryl-CoA
?
show the reaction diagram
different co-substrates tested
-
-
?
3-methylcrotonyl-CoA
?
show the reaction diagram
different co-substrates tested
-
-
?
3-methylglutaconyl-CoA
?
show the reaction diagram
crotonyl-CoA
?
show the reaction diagram
different co-substrates tested
-
-
?
trans-3-methylglutaconyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA
show the reaction diagram
-
-
-
-
?
trans-3-methylglutaconyl-CoA + H2O
(S)-3-hydroxymethylglutaryl-CoA
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-3-Hydroxy-3-methylglutaryl-CoA
?
show the reaction diagram
(S)-3-hydroxy-3-methylglutaryl-CoA
trans-3-methylglutaconyl-CoA + H2O
show the reaction diagram
trans-3-methylglutaconyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-methylcrotonyl-CoA
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crotonyl-CoA
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Mersalyl
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-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0083
(E)-3-methylglutaconyl-CoA
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-
0.0024 - 0.04
(E)-glutaconyl-CoA
2.25
(R,S)-3-hydroxy-3-methylglutaryl-CoA
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-
0.03
(S)-3-hydroxy-3-methylglutaryl-CoA
-
0.05
(S)-3-hydroxyglutaryl-CoA
dehydration
0.0069 - 0.0094
(S)-3-hydroxymethylglutaryl-CoA
55.2
3-hydroxybutyryl-CoA
-
-
0.347
3-methylcrotonyl-CoA
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-
0.01
3-methylglutaconyl-CoA
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12.1
crotonyl-CoA
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-
0.0291 - 0.08
trans-3-methylglutaconyl-CoA
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.1
(E)-3-methylglutaconyl-CoA
Homo sapiens
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-
1.4 - 18
(E)-glutaconyl-CoA
0.26
(R,S)-3-hydroxy-3-methylglutaryl-CoA
Homo sapiens
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60
(S)-3-hydroxy-3-methylglutaryl-CoA
Acinetobacter sp.
Q3HW12
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13
(S)-3-hydroxyglutaryl-CoA
Acinetobacter sp.
Q3HW12
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1.7
3-hydroxybutyryl-CoA
Homo sapiens
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-
2.9
3-methylcrotonyl-CoA
Homo sapiens
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-
138
3-methylglutaconyl-CoA
Acinetobacter sp.
Q3HW12
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6.8
crotonyl-CoA
Homo sapiens
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-
0.00086 - 2.1
trans-3-methylglutaconyl-CoA
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0317
3-methylcrotonyl-CoA
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pH 7.09, 25°C, wild-type enzyme
0.0949
crotonyl-CoA
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pH 7.9, 25°C, wild-type enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.5
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pH 6.0: about 80% of maximal activity, pH 8.5: about 50% of maximal activity
7 - 7.4
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kinetic constants determined at pH 7.4, direct nonisotopic activity assay in human skin fibroblasts at pH 7.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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activity assay in human skin fibroblasts at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
cultured
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28680
deduced from amino acid sequence
28800
MALDI-TOF
89980
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mass spectroscopy, RNA free AUH
109000
gel filtration
221400
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mass spectroscopy, in the presence of a long RNA containing 24 repeats of the AUUU motif, (AUUU)24A
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer or trimer
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AUH trimer dimerizes upon binding to one molecule of a long RNA containing 24 repeats of the AUUU motif, (AUUU)24A, determined by mass-spectroscopy
homotetramer
trimer
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mainly exists as a trimer in solution, determined by mass-spectroscopy
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AUH is crystallized with a long RNA containing 24 repeats of the AUUU motif. AUH structure is determined as an asymmetric dimer of trimers with a kink in the alignment of the trimer axes, resulting in the formation of two clefts with significantly different sizes
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
from cell-free extracts of isovalerate-grown cells of Acinetobacter strain IVS-B by gel-filtration and SDS-PAGE
gel-filtration and SDS-PAGE
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli, amino acid sequence determined, membership to the crotonase/isomerase super family classified by comparing protein seqences, up to 50% identity to amino acid sequences of more than 100 prokaryotic enoyl-CoA hydratases, 30% homology to the gene product of human AUH gene
gene AUH, genotyping
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overexpression in Escherichia coli using the pMAL-c2 expression vector
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A240V
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site-directed mutagenesis, nucleotide exchange C719T
E138A
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inactive mutant enzyme
E138D
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the ratio of turnover number to KM-value is 9fold lower than the wild-type ratio
E138Q
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the ratio of turnover number to KM-value is 3600fold lower than the wild-type ratio
G118E
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no activity with crotonyl-CoA, methylcrotonyl-CoA and methylglutaconyl-CoA
E138A
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inactive mutant enzyme
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E138D
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the ratio of turnover number to KM-value is 9fold lower than the wild-type ratio
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E138Q
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the ratio of turnover number to KM-value is 3600fold lower than the wild-type ratio
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G118E
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no activity with crotonyl-CoA, methylcrotonyl-CoA and methylglutaconyl-CoA
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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