EC Number   |
Protein Variants |
Reference |
|---|
    4.2.1.17 | A3D/F279S |
naturally occuring mutations, identification of heterozygous ECHS1 mutations c.836T>C (novel) (p.F279S) and and c.8C>A (p.A3D) identified by whole exome sequencing, lethal neonatal case. SCEH deficiency is confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient has a severe neonatal course with elevated blood and cerebrospinal fluid (CSF) lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid is markedly elevated as are metabolites of the three branched-chain ketoacids on urine organic acids analysis. These urine metabolites notably decrease when lactic acidosis decreases in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity is deficient, but PDC and 2-oxoglutarate dehydrogenase complex activities in cultured fibroblasts are normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts is suggestive of slightly reduced PDC activity relative to control range in mitochondria |
748661 |
| 4.2.1.17 | A98P |
kcat is decreased 3400fold compared to wild type and KM is increased 13fold, mutant enzyme has a severely compromised ability for catalyzing the formation of (3R)-3-hydroxybutanoyl-CoA |
650113 |
| 4.2.1.17 | E144A |
kcat for trans-2-hexenoyl-CoA is 1733fold lower than wild-type value |
649889 |
| 4.2.1.17 | E144A |
site-directed mutagenesis, the mutant shows a 1000fold reduced activity compared to the wild-type enzyme |
697212 |
| 4.2.1.17 | E144A/Q162L |
kcat for trans-2-hexenoyl-CoA is 12417fold lower than wild-type value. The point mutations E144A and Q162L by themselves apparently do not cause structural rearrangements of the active site helix, but when both residues are changed, the active site geometry changes |
649889 |
| 4.2.1.17 | E144D |
60fold decreases in kcat with little change in KM |
650113 |
| 4.2.1.17 | E144Q |
3000fold decreases in kcat with little change in KM. The mutant is unable to catalyze the formation of (3R)-3-hydroxybutanoyl-CoA even when the incubation is extended to 4 days |
650113 |
| 4.2.1.17 | E164A |
kcat for trans-2-hexenoyl-CoA is 1709fold lower than wild-type value |
649889 |
| 4.2.1.17 | E164A |
site-directed mutagenesis, the mutant shows a 1000fold reduced activity compared to the wild-type enzyme |
697212 |
| 4.2.1.17 | E164D |
1200fold decreases in kcat with little change in KM. First-order rate constant for the formation of (3R)-3-hydroxybutanoyl-CoA is similar to wild-type value |
650113 |
