EC Number |
General Information |
Reference |
---|
1.1.1.357 | evolution |
3alpha-HSOR is a member of the aldo-keto reductase superfamily |
763094 |
1.1.1.357 | evolution |
enzyme 3alpha-HSD/CR belongs to the short chain dehydrogenase/ reductase (SDR) superfamily |
742260, 743632 |
1.1.1.357 | evolution |
enzyme AKR1C14 belongs to the aldo-keto reductase family |
763517 |
1.1.1.357 | evolution |
human 3alpha-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid dehydrogenase (20alpha-HSD) and there is only one amino acid difference (residue 54) that is located in their steroid binding pockets. 20alpha-HSD displays a distinctive ability in transforming progesterone to 20alpha-hydroxy-progesterone |
743179 |
1.1.1.357 | evolution |
the enzyme belongs to the AKR1C subfamily, the members of which catalyze the reduction of ketosteroids and ketoprostaglandins |
739797 |
1.1.1.357 | malfunction |
downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth |
740017 |
1.1.1.357 | malfunction |
loss of hydrogen bonding with NADH upon the Y153F mutation results in increased enthalpy change, partially compensated by increased entropy change. The NADH binding affinity of K157A mutant is much lower than that of the wild-type, mainly due to loss of a hydrogen bond. The decreased affinity results in decreased kcat. Compared to the wild-type, the mutants S114A and Y153F show higher Km and lower kcat values in both oxidation and reduction reactions. Simultaneous mutation of S114A and Y153F results in a significant decrease in kcat relative to the single mutant |
760734 |
1.1.1.357 | malfunction |
mutation at P185 in the hinge region and T188 in the loop causes a significant increase in the Kd value for NADH. Mutants P185A, P185G, T188A, and T188S show an increase the dissociation of the nucleotide cofactor, thereby increasing the rate of release of the product and producing the rate-limiting step in the hydride transfer |
743632 |
1.1.1.357 | malfunction |
the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone (PROG) and testosterone (T) reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Changes in brain levels of PROG metabolites have been detected in Alzheimer's disease (AD) mouse models, such as the 3xTg-AD mouse |
763094 |
1.1.1.357 | malfunction |
the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone (PROG) and testosterone (T) reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Low plasma testosterone levels are significantly associated with increased risk of Alzheimer's disease in elderly men, while higher free testosterone levels in women are associated with lower cerebral Abeta positivity |
763094 |