EC Number   |
Protein Variants |
Reference |
|---|
   1.14.14.25 | A1309C |
destroys its heme structure, resulting in the complete lack of cholesterol 24-hydroxylase activity |
705825 |
| 1.14.14.25 | K422A |
site-directed mutagenesis, the K422A mutant retains the ability to be activated by EFV, although to a slightly lower extent than wild-type CYP46A1. The cholesterol-bound K422A mutant also shows cooperativity similar to cholesterol-bound wild-type CYP46A1. Binding to NADPH cytochrome P450 oxidoreductase is reduced compared to the wild-type |
736502 |
| 1.14.14.25 | K94A |
site-directed mutagenesis, the K94A replacement produces inactive P420 protein |
736502 |
| 1.14.14.25 | more |
brains from mice lacking 24-hydroxylase excrete cholesterol more slowly, and the tissue compensates by suppressing the mevalonate pathway, this suppression causes a defect in learning, 24-hydroxylase knockout mice exhibit severe deficiencies in spatial, associative, and motor learning, and in hippocampal long-term potentiation, the effects of genetic elimination of 24-hydroxylase on long-term potentiation are reversed by a 20-min treatment with geranylgeraniol but not by cholesterol, phenotype, overview |
676852 |
| 1.14.14.25 | more |
construction of an mutant CYP46A1, in which the first 50 N-terminal amino acid residues are deleted, and a His4 tag is added at the C-terminus. The truncation removed a 23-residue transmembrane-anchoring domain and renders this membrane P450 more soluble compared to the wild-type, overview |
689814 |
| 1.14.14.25 | more |
construction of knockout mice, concentration and the pool of cholesterol in the CNS is unchanged compared with control animals, but synthesis is suppressed by about 25% in the CYP46a1-deficient mice, but not in those lacking 7a- or 27-hydroxylase activity, the concentrations of 24S-hydroxycholesterol in the brain and plasma decline to very low levels, the CNS in the mouse apparently responds appropriately to loss of this excretory pathway by suppressing endogenous synthesis by an amount exactly equal to the mass of cholesterol that would normally be excreted as 24S-hydroxycholesterol |
671173 |
| 1.14.14.25 | more |
construction of truncated enzyme mutant DELTA(3-27)CYP46A1 |
736502 |
| 1.14.14.25 | more |
determination of single nucleotide polymorphisms in North American Caucasians and Caribbean Hispanic Alzheimer patients, overview |
660012 |
| 1.14.14.25 | more |
four truncation mutants: all lack the N-terminal transmembrane region (residues 3 27), and, in addition, DELTA46A1 has a 4 His-tag fused to the C-terminus, HDELTA46A1 has the N-terminal 4 His-tag, HDELTA46A1DELTA has a 4 His-tag at the N-terminus and does not contain a proline-rich region at the C-terminus (residues 494 499), and DELTA46A1DELTA lacks the C-terminal proline-rich region. Truncated enzymes have moderately decreased catalytic efficiencies for either cholesterol or 24S-hydroxycholesterol or both, whereas their substrate-binding constants are either unchanged or decreased 2fold.The two forms, DELTA64A1DELTA and HDELTA46A1DELTA both lacking the C-terminal proline-rich region are good candidates for future crystallographic studies because they contain only 0.3 0.8% of high molecular weight aggregates and their catalytic efficiencies are decreased no more than 2.3fold |
657671 |
| 1.14.14.25 | more |
knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1. Expression of shRNA sequence that inhibits CYP46A1 expression in vitro and in vivo, phenotype, overview. CYP46A1 restoration in the striatum improves the motor phenotype of R6/2 mice |
-, 735877 |
