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- Name help_outline cholesterol Identifier CHEBI:16113 (Beilstein: 2060565; CAS: 57-88-5) help_outline Charge 0 Formula C27H46O InChIKeyhelp_outline HVYWMOMLDIMFJA-DPAQBDIFSA-N SMILEShelp_outline C1[C@@]2([C@]3(CC[C@]4([C@]([C@@]3(CC=C2C[C@H](C1)O)[H])(CC[C@@]4([C@H](C)CCCC(C)C)[H])[H])C)[H])C 2D coordinates Mol file for the small molecule Search links Involved in 63 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NAD+ Identifier CHEBI:57540 (Beilstein: 3868403) help_outline Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-NNYOXOHSSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,186 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline cholest-5-en-3-one Identifier CHEBI:63906 (CAS: 601-54-7) help_outline Charge 0 Formula C27H44O InChIKeyhelp_outline GGCLNOIGPMGLDB-GYKMGIIDSA-N SMILEShelp_outline [H][C@@]1(CC[C@@]2([H])[C@]3([H])CC=C4CC(=O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCCC(C)C 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADH Identifier CHEBI:57945 (Beilstein: 3869564) help_outline Charge -2 Formula C21H27N7O14P2 InChIKeyhelp_outline BOPGDPNILDQYTO-NNYOXOHSSA-L SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,116 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:35459 | RHEA:35460 | RHEA:35461 | RHEA:35462 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Cholesterol is not an essential source of nutrition for Mycobacterium tuberculosis during infection.
Yang X., Gao J., Smith I., Dubnau E., Sampson N.S.
Rv1106c (hsd; 3β-hydroxysteroid dehydrogenase) is required by Mycobacterium tuberculosis for growth on cholesterol as a sole carbon source, whereas Rv3409c is not. Mutation of Rv1106c does not reduce Mycobacterium tuberculosis growth in infected macrophages or guinea pigs. We conclude that cholest ... >> More
Rv1106c (hsd; 3β-hydroxysteroid dehydrogenase) is required by Mycobacterium tuberculosis for growth on cholesterol as a sole carbon source, whereas Rv3409c is not. Mutation of Rv1106c does not reduce Mycobacterium tuberculosis growth in infected macrophages or guinea pigs. We conclude that cholesterol is not required as a nutritional source during infection. << Less
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Genetic identification of HSD-1, a conserved steroidogenic enzyme that directs larval development in Caenorhabditis elegans.
Patel D.S., Fang L.L., Svy D.K., Ruvkun G., Li W.
In C. elegans, steroid hormones function in conjunction with insulin/IGF-1-like signaling in promoting reproductive development over entry into the diapausal dauer stage. The NCR-1 and -2 (NPC1-related) intracellular cholesterol transporters function redundantly in preventing dauer arrest, presuma ... >> More
In C. elegans, steroid hormones function in conjunction with insulin/IGF-1-like signaling in promoting reproductive development over entry into the diapausal dauer stage. The NCR-1 and -2 (NPC1-related) intracellular cholesterol transporters function redundantly in preventing dauer arrest, presumably by regulating the availability of substrates for steroid hormone synthesis. We have identified hsd-1 as a new component of this cholesterol trafficking/processing pathway, using an ncr-1 enhancer screen. HSD-1 is orthologous to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerases (3beta-HSDs), which are key steroidogenic enzymes in vertebrates, and is exclusively expressed in two neuron-like XXX cells that are crucial in preventing dauer arrest, suggesting that it is involved in biosynthesis of dauer-preventing steroid hormones. The hsd-1 null mutant displays defects in inhibiting dauer arrest: it forms dauers in the deletion mutant backgrounds of ncr-1 or daf-28/insulin; as a single mutant, it is hypersensitive to dauer pheromone. We found that hsd-1 defects can be rescued by feeding mutant animals with several steroid intermediates that are either downstream of or in parallel to the 3beta-HSD function in the dafachronic acid biosynthetic pathway, suggesting that HSD-1 functions as a 3beta-HSD. Interestingly, sterols that rescued hsd-1 defects also bypassed the need for the NCR-1 and/or -2 functions, suggesting that HSD-1-mediated steroid hormone production is an important functional output of the NCR transporters. Finally, we found that the HSD-1-mediated signal activates insulin/IGF-I signaling in a cell non-autonomous fashion, suggesting a novel mechanism for how these two endocrine pathways intersect in directing development. << Less
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Rv1106c from Mycobacterium tuberculosis is a 3beta-hydroxysteroid dehydrogenase.
Yang X., Dubnau E., Smith I., Sampson N.S.
New approaches are required to combat Mycobacterium tuberculosis (Mtb), especially the multi-drug resistant and extremely drug resistant organisms (MDR-TB and XDR-TB). There are many reports that mycobacteria oxidize 3beta-hydroxysterols to 3-ketosteroids, but the enzymes responsible for this acti ... >> More
New approaches are required to combat Mycobacterium tuberculosis (Mtb), especially the multi-drug resistant and extremely drug resistant organisms (MDR-TB and XDR-TB). There are many reports that mycobacteria oxidize 3beta-hydroxysterols to 3-ketosteroids, but the enzymes responsible for this activity have not been identified in mycobacterial species. In this work, the Rv1106c gene that is annotated as a 3beta-hydroxysteroid dehydrogenase in Mtb has been cloned and heterologously expressed. The purified enzyme was kinetically characterized and found to have a pH optimum between 8.5 and 9.5. The enzyme, which is a member of the short chain dehydrogenase superfamily, uses NAD+ as a cofactor and oxidizes cholesterol, pregnenolone, and dehydroepiandrosterone to their respective 3-keto-4-ene products. The enzyme forms a ternary complex with NAD+ binding before the sterol. The enzyme shows no substrate preference for dehydroepiandrosterone versus pregnenolone with second-order rate constants (kcat/Km) of 3.2 +/- 0.4 and 3.9 +/-0.9 microM-1 min-1, respectively, at pH 8.5, 150 mM NaCl, 30 mM MgCl2, and saturating NAD+. Trilostane is a competitive inhibitor of dehydroepiandrosterone with a Ki of 197 +/-8 microM. The expression of the 3beta-hydroxysteroid dehydrogenase in Mtb is intracellular. Disruption of the 3beta-hydroxysteroid dehydrogenase gene in Mtb abrogates mycobacterial cholesterol oxidation activity. These data are consistent with the Rv1106c gene being the one responsible for 3beta-hydroxysterol oxidation in Mtb. << Less
Biochemistry 46:9058-9067(2007) [PubMed] [EuropePMC]
This publication is cited by 7 other entries.