Cytochrome P450 125A4, the Third Cholesterol C-26 Hydroxylase from Mycobacterium smegmatis
| Autor: | Maggie La, Christopher A. Waddling, Paul R. Ortiz de Montellano, Daniel J. Frank |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Medical Biochemistry and Metabolomics Crystallography X-Ray Biochemistry Substrate Specificity chemistry.chemical_compound Gene Knockout Techniques Cytochrome P-450 Enzyme System Models Catalytic Domain Site-Directed Cholesterol 7-alpha-Hydroxylase chemistry.chemical_classification 0303 health sciences Crystallography biology Mycobacterium smegmatis 030302 biochemistry & molecular biology Bacterial 3. Good health Spectrophotometry lipids (amino acids peptides and proteins) Biochemistry & Molecular Biology Cholesterol 7 alpha-hydroxylase Article Microbiology Mycobacterium tuberculosis Medicinal and Biomolecular Chemistry 03 medical and health sciences Rare Diseases Bacterial Proteins Oxidoreductase Tuberculosis Structural Homology 030304 developmental biology Cholesterol Protein Molecular Cytochrome P450 biology.organism_classification Sterol Hydroxycholesterols Kinetics Enzyme Genes chemistry Amino Acid Substitution Mutagenesis Genes Bacterial Structural Homology Protein X-Ray biology.protein Mutagenesis Site-Directed Biochemistry and Cell Biology |
| Zdroj: | Biochemistry Biochemistry, vol 54, iss 46 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Msmeg) can grow on cholesterol as the sole carbon source. In Mtb the utilization of cholesterol can be initiated by CYP125A1 or CYP142A1 and in Msmeg by the orthologous CYP125A3 and CYP142A2. Double knockout of the two enzymes in Mtb prevents its growth on cholesterol, but the double knockout of Msmeg is still able to grow, albeit at a slower rate. We report here that Msmeg has a third enzyme, CYP125A4, that also oxidizes cholesterol, although it has a much higher activity for the oxidation of 7α-hydroxycholesterol. The ability of Msmeg CYP125A4 (and Mtb CYP125A1) to oxidize 7α-hydroxycholesterol is due, at least in part, to the presence of a smaller amino acid side chain facing C-7 of the sterol substrate than in CYP125A3. The ability to oxidize 7-substituted steroids broadens the range of sterol carbon sources for growth, but even more importantly in Mtb, additional biological effects are possible due to the potent immunomodulatory activity of 7α,26-dihydroxycholesterol. |
| Databáze: | OpenAIRE |
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