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Information on EC 4.2.1.119 - enoyl-CoA hydratase 2 and Organism(s) Homo sapiens
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4.2.1.119 enoyl-CoA hydratase 2IUBMB Comments
This enzyme catalyses a hydration step in peroxisomal beta-oxidation. The human multifunctional enzyme type 2 (MFE-2) is a 79000 Da enzyme composed of three functional units: (3R)-hydroxyacyl-CoA dehydrogenase, 2-enoyl-CoA hydratase 2 and sterol carrier protein 2-like units . The enzymes from Aeromonas caviae and Arabidopsis thaliana are monofunctional enzymes. 2-Enoyl-CoA hydratase 3 from Candida tropicalis is a part from multifunctional enzyme type 2 .
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Word Map
- 4.2.1.119
-
beta-oxidation
- enoyl-coas
- polyhydroxyalkanoate
- mfe-2s
- trans-2-enoyl-coa
-
r-3-hydroxyacyl-coas
- aconitate
-
phajs
- caviae
-
3r-hydroxyacyl-coa
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even-numbered
- biotechnology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
hydratase 2, multifunctional enzyme type 2, phaj1, phaj4, atech2, enoyl-coa hydratase 2, phaj1pp, phaj1pa, phajyb4, d-3-hydroxyacyl-coa hydro-lyase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-enoyl-CoA hydratase 2
MFE-2
-
peroxisomal hydratase 2 together with (3R)-hydroxyacyl-CoA dehydrogenase is present as multifunctional enzyme
2-enoyl-CoA hydratase 2
-
domain of multifunctional enzyme type 2 (MFE-2), (3R)-hydroxyacyl-CoA dehydrogenase/2-enoyl-CoA hydratase 2
2-enoyl-CoA hydratase 2
the enzyme is the middle part of the mammalian peroxisomal multifunctional enzyme type 2 (MFE-2)
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(3R)-3-hydroxyacyl-CoA hydro-lyase
This enzyme catalyses a hydration step in peroxisomal beta-oxidation. The human multifunctional enzyme type 2 (MFE-2) is a 79000 Da enzyme composed of three functional units: (3R)-hydroxyacyl-CoA dehydrogenase, 2-enoyl-CoA hydratase 2 and sterol carrier protein 2-like units [1]. The enzymes from Aeromonas caviae [4] and Arabidopsis thaliana [5] are monofunctional enzymes. 2-Enoyl-CoA hydratase 3 from Candida tropicalis is a part from multifunctional enzyme type 2 [3].
CAS REGISTRY NUMBER
COMMENTARY
9027-13-8
cf. EC 4.2.1.17
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
(2E)-2-enoyl-CoA + H2O
(3R)-3-hydroxyacyl-CoA
peroxisomal multifunctional enzyme type 2 (MFE-2) is a 79000 Da enzyme composed of three functional units: (3R)-hydroxyacyl-CoA dehydrogenase, 2-enoyl-CoA hydratase 2 and sterol carrier protein 2-like units. It catalyzes the second and third steps of peroxisomal beta-oxidation, and its importance in human lipid metabolism is shown by the severe clinical symptoms (dysmorphic features, such as macrocephaly and large fontanelles, hypotonia, seizures, etc.) in patients having defects in the gene encoding MFE-2. Typical biochemical observations include a high ratio of C26:0 to C22:0 fatty acids and elevated levels of pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) in the patients plasma and fibroblasts, indicating the significance of MFE-2 in the breakdown of very-long-chain and alpha-methylbranched-chain fatty acids. The patients also have high levels of di- and trihydroxycholestanoic acids, which are precursors of bile acids, showing that MFE-2 also participates in bile acid synthesis
-
-
?
(R)-3-hydroxyoctanoyl-CoA
octenoyl-CoA + H2O
-
no activity with (S)-3-hydroxyoctanoyl-CoA
-
-
r
crotonyl-CoA + H2O
(R)-3-hydroxybutanoyl-CoA
-
very low activity with crotonyl-CoA
-
-
r
dec-2-enoyl-CoA + H2O
(R)-3-hydroxydecanoyl-CoA
-
9-12% of the activity with hexenoyl-CoA, depending on preparation
-
-
?
dodec-2-enoyl-CoA + H2O
(R)-3-hydroxydodecanoyl-CoA
-
4-5% of the activity with hexenoyl-CoA, depending on preparation
-
-
?
oct-2-enoyl-CoA + H2O
(R)-3-hydroxyoctanoyl-CoA
-
30-40% of the activity with hexenoyl-CoA, depending on preparation
-
-
r
additional information
?
-
-
peroxisomal hydratase 2 together with (3R)-hydroxyacyl-CoA dehydrogenase, and peroxisomal hydratase 1 together with (3S)-hydroxyacyl-CoA dehydrogenase, are present as multifunctional enzymes. When present simultaneously in peroxisomes, beta-oxidation has two stereochemical possibilities
-
-
?
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
(2E)-2-enoyl-CoA + H2O
(3R)-3-hydroxyacyl-CoA
peroxisomal multifunctional enzyme type 2 (MFE-2) is a 79000 Da enzyme composed of three functional units: (3R)-hydroxyacyl-CoA dehydrogenase, 2-enoyl-CoA hydratase 2 and sterol carrier protein 2-like units. It catalyzes the second and third steps of peroxisomal beta-oxidation, and its importance in human lipid metabolism is shown by the severe clinical symptoms (dysmorphic features, such as macrocephaly and large fontanelles, hypotonia, seizures, etc.) in patients having defects in the gene encoding MFE-2. Typical biochemical observations include a high ratio of C26:0 to C22:0 fatty acids and elevated levels of pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) in the patients plasma and fibroblasts, indicating the significance of MFE-2 in the breakdown of very-long-chain and alpha-methylbranched-chain fatty acids. The patients also have high levels of di- and trihydroxycholestanoic acids, which are precursors of bile acids, showing that MFE-2 also participates in bile acid synthesis
-
-
?
additional information
?
-
-
peroxisomal hydratase 2 together with (3R)-hydroxyacyl-CoA dehydrogenase, and peroxisomal hydratase 1 together with (3S)-hydroxyacyl-CoA dehydrogenase, are present as multifunctional enzymes. When present simultaneously in peroxisomes, beta-oxidation has two stereochemical possibilities
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 10
-
pH dependence experiment is performed in 200 mM potassium phosphate buffer at pH values varying from 5 to 10
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
2-enoyl-CoA hydratase 2 is the middle part of the mammalian peroxisomal multifunctional enzyme type 2 (MFE-2)
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
peroxisomal hydratase 2 together with (3R)-hydroxyacyl-CoA dehydrogenase, and hydratase 1 together with (3S)-hydroxyacyl-CoA dehydrogenase, are present as multifunctional enzymes. When present simultaneously in peroxisomes, beta-oxidation has two stereochemical possibilities
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
inactivating mutations of multifunctional enzyme type 2 hydratase lead to D-bifunctional protein deficiency type II
additional information
-
MFE2 hydratase is R-specific, while MFE1 hydratase is S-specific
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). DHB4_HUMAN
736
0
79686
Swiss-Prot
Mitochondrion (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
-
x * 45000, HsMFE-2(dhdelta), HsMFE-2(dhdelta, E366A), HsMFE-2(dhdelta, D510A), SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 45000, HsMFE-2(dhdelta), HsMFE-2(dhdelta, E366A), HsMFE-2(dhdelta, D510A), SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapor diffusion method, crystal structure to 3 A resolution. MFE-2 has a two-domain subunit structure with a C-domain complete hot-dog fold housing the active site, and an N-domain incomplete hot-dog fold housing the cavity for the aliphatic acyl part of the substrate molecule. The ability of human hydratase 2 to utilize such bulky compounds which are not physiological substrates for the fungal ortholog, e.g. CoA esters of C26 fatty acids, pristanic acid and di/trihydroxycholestanoic acids, is explained by a large hydrophobic cavity formed upon the movements of the extremely mobile loops IIII in the N-domain. In the unliganded form of human hydratase 2, however, the loop I blocks the entrance of fatty enoyl-CoAs with chain-length above C8
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A427V
-
site-directed mutagenesis, the mutation does not affect the enzyme, the mutant shows a slight increase in activity
D370A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
D490A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
D510Y
-
site-directed mutagenesis, inactive mutant, the mutation disrupts active site architecture
D517A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
E366G
-
site-directed mutagenesis, inactive mutant, the mutation disrupts dimerization
E408A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
G16S
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
G533R
-
site-directed mutagenesis, inactive mutant, the mutation disrupts ligand interaction
H406A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
H532A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
H532R
-
site-directed mutagenesis, inactive mutant, the mutation disrupts active site architecture
I516T
-
site-directed mutagenesis, the mutation disrupts dimerization, the mutant shows reduced activity
L405P
-
site-directed mutagenesis, inactive mutant, the mutation disrupts ligand interaction
N457Y
-
site-directed mutagenesis, the mutation disrupts domain folding, the mutant shows reduced activity
P529L
-
site-directed mutagenesis, inactive mutant, the mutation disrupts active site architecture
R506C
-
site-directed mutagenesis, inactive mutant, the mutation disrupts dimerization
R506H
-
site-directed mutagenesis, inactive mutant, the mutation disrupts dimerization
Y410A
-
reduced specific acitivity of 2-enoyl-CoA hydratase 2 when expressed in Saccharomyces cerevisiae
additional information
additional information
-
mutant constructs are tested for complementation in Saccharomyces cerevisiae
additional information
-
site-directed mutagenesis is used for construction of mutants corresponding to 17 reported missense mutations of multifunctional enzyme type 2 hydratase. Some mutants are almost or completely inactive causing the D-bifunctional protein deficiency type II
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant GFP-tagged hydratase domains of multifunctional enzyme type 2 hydratase from Escherichia coli strain JM109 by anion exchange chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant hydratase domains of multifunctional enzyme type 2 hydratase as GFP-tagged protein in Escherichia coli strain JM109
-
wild type (HsMFE-2) and its variants are expressed in Saccharomyces cerevisiae, the recombinant HsMFE-2(dhdelta) and its variants are expressed in Escherichia coli BL21(DE3)pLysS
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jiang, L.L.; Kobayashi, A.; Matsuura, H.; Fukushima, H.; Hashimoto, T.
Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase
J. Biochem.
120
624-632
1996
Homo sapiens
Qin, Y.M.; Haapalainen, A.M.; Kilpelainen, S.H.; Marttila, M.S.; Koski, M.K.; Glumoff, T.; Novikov, D.K.; Hiltunen, J.K.
Human peroxisomal multifunctional enzyme type 2: site-directed mutagenesis studies show the importance of two protic residues for 2-enoyl-CoA hydratase 2 activity
J. Biol. Chem.
275
4965-4972
2000
Homo sapiens
Kristian Koski, M.; Haapalainen, A.M.; Hiltunen, J.K.; Glumoff, T.
Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2
J. Mol. Biol.
345
1157-1169
2005
Homo sapiens (P51659), Homo sapiens
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