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Literature summary for 1.1.1.35 extracted from

  • Xu, Y.; Li, H.; Jin, Y.H.; Fan, J.; Sun, F.
    Dimerization interface of 3-hydroxyacyl-CoA dehydrogenase tunes the formation of its catalytic intermediate (2014), PLoS ONE, 9, e95965.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.1.1.35

Cloned(Commentary)

Cloned (Comment) Organism
gene F54C8.1, recombinant expression of C-terminally GST-tagged enzyme in Escherichia coli strain BL21(DE3) Caenorhabditis elegans

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant detagged wild-type enzyme, crystals are grown by hanging drop method from 23% PEG 3350, 0.2 M sodium chloride, 0.1M N,N-bis (2-hydroxyethyl)glycine, pH 8.0, X-ray diffraction structure determination and analysis at 2.20 A resolution, molecular replacement with the human HAD structure as search model, PDB ID 3had Caenorhabditis elegans

Protein Variants

Protein Variants Comment Organism
D45G/Y214H a naturally occuring enzyme mutation causing human disease Homo sapiens
M176V a naturally occuring enzyme mutation causing human disease Homo sapiens
additional information c.547-3_549delbis and IVS6-2a.gc are naturally occuring enzyme mutations causing human disease. Mapping of disease-relevant HAD mutations onto the crystal structure of human HAD, PDB ID 1F0Y Homo sapiens
P246L a naturally occuring enzyme mutation causing human disease Homo sapiens
R204A site-directed mutagenesis, the mutant with attenuated interactions on the dimerization interface still maintains a dimerization form, but the enzymatic activity is significantly decreased compared the wild-type Caenorhabditis elegans
R204A/Y209A site-directed mutagenesis, the mutant with attenuated interactions on the dimerization interface still maintains a dimerization form, but the enzymatic activity is significantly decreased compared the wild-type Caenorhabditis elegans
R224X a naturally occuring enzyme mutation causing human disease Homo sapiens
Y209A site-directed mutagenesis, the mutant with attenuated interactions on the dimerization interface still maintains a dimerization form, but the enzymatic activity is significantly decreased compared the wild-type Caenorhabditis elegans

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0505
-
 (R)-3-hydroxyacyl-CoA recombinant mutant Y209A, pH 7.0, 25°C Caenorhabditis elegans
0.0721
-
 (R)-3-hydroxyacyl-CoA recombinant wild-type enzyme, pH 7.0, 25°C Caenorhabditis elegans
0.0833
-
 (R)-3-hydroxyacyl-CoA recombinant mutant R204A, pH 7.0, 25°C Caenorhabditis elegans
0.1157
-
 (R)-3-hydroxyacyl-CoA recombinant mutant R204A/Y209A, pH 7.0, 25°C Caenorhabditis elegans

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrial matrix
-
 Homo sapiens 5759
-
mitochondrial matrix
-
 Caenorhabditis elegans 5759
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-3-hydroxyacyl-CoA + NAD+ Homo sapiens
-
 3-oxoacyl-CoA + NADH + H+
-
 ?
(S)-3-hydroxyacyl-CoA + NAD+ Caenorhabditis elegans
-
 3-oxoacyl-CoA + NADH + H+
-
 r

Organism

Organism UniProt Comment Textmining
Caenorhabditis elegans P34439
-
-
Homo sapiens Q16836
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant C-terminally GST-tagged enzyme from Escherichia coli strain BL21(DE3) by glutathione affinity and anion exchange chromatography, with cleavage of the GST-tag Caenorhabditis elegans

Reaction

Reaction Comment Organism Reaction ID
(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH + H+ structure-function analysis and catalytic mechanism, overview Homo sapiens
a
(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH + H+ structure-function analysis using the crystal structure, PDB ID 4j0f, and catalytic mechanism, overview Caenorhabditis elegans
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(R)-3-hydroxyacyl-CoA + NAD+ cf. EC 1.1.1.36 Caenorhabditis elegans 3-oxoacyl-CoA + NADH + H+
-
 r
(S)-3-hydroxyacyl-CoA + NAD+
-
 Homo sapiens 3-oxoacyl-CoA + NADH + H+
-
 ?
(S)-3-hydroxyacyl-CoA + NAD+
-
 Caenorhabditis elegans 3-oxoacyl-CoA + NADH + H+
-
 r

Subunits

Subunits Comment Organism
homodimer
-
 Homo sapiens
homodimer structure-function analysis using the crystal structure, PDB ID 4j0f Caenorhabditis elegans

Synonyms

Synonyms Comment Organism
F54C8.1
-
 Caenorhabditis elegans
HAD
-
 Homo sapiens
HAD
-
 Caenorhabditis elegans
HADH
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Caenorhabditis elegans

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2 8 (R)-3-hydroxyacyl-CoA recombinant mutant R204A, pH 7.0, 25°C Caenorhabditis elegans
10
-
 (R)-3-hydroxyacyl-CoA recombinant mutant R204A/Y209A, pH 7.0, 25°C Caenorhabditis elegans
17
-
 (R)-3-hydroxyacyl-CoA recombinant mutant Y209A, pH 7.0, 25°C Caenorhabditis elegans
45
-
 (R)-3-hydroxyacyl-CoA recombinant wild-type enzyme, pH 7.0, 25°C Caenorhabditis elegans

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
 assay at Caenorhabditis elegans

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Homo sapiens
NAD+
-
 Caenorhabditis elegans
NADH
-
 Caenorhabditis elegans

General Information

General Information Comment Organism
evolution Caenorhabditis elegans HAD is highly conserved to human HAD Homo sapiens
evolution Caenorhabditis elegans HAD is highly conserved to human HAD Caenorhabditis elegans
malfunction mutantions with attenuated interactions on the dimerization interface significantly decrease the enzyme activity compared to the wild-type. Such reduced activities are in consistency with the reduced ratios of the catalytic intermediate formation. Further molecular dynamics simulations results reveal that the alteration of the dimerization interface will increase the fluctuation of a distal region that plays an important role in the substrate binding. The increased fluctuation decreases the stability of the catalytic intermediate formation, and therefore the enzymatic activity is attenuated Caenorhabditis elegans
malfunction numerous human diseases are found related to mutations at HAD dimerization interface that is away from the catalytic pocket Homo sapiens
metabolism 3-hydroxyacyl-CoA dehydrogenase catalyzes the third step in fatty acid beta-oxidation Homo sapiens
metabolism 3-hydroxyacyl-CoA dehydrogenase catalyzes the third step in fatty acid beta-oxidation Caenorhabditis elegans
additional information molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview Homo sapiens
additional information molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview Caenorhabditis elegans

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
90
-
 (R)-3-hydroxyacyl-CoA recombinant mutant R204A/Y209A, pH 7.0, 25°C Caenorhabditis elegans
300
-
 (R)-3-hydroxyacyl-CoA recombinant mutants R204A and Y209A, pH 7.0, 25°C Caenorhabditis elegans
600
-
 (R)-3-hydroxyacyl-CoA recombinant wild-type enzyme, pH 7.0, 25°C Caenorhabditis elegans