Enzymes
| UniProtKB help_outline | 2 proteins |
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- Name help_outline (25S)-3-oxocholest-4-en-26-oyl-CoA Identifier CHEBI:83819 Charge -4 Formula C48H72N7O18P3S InChIKeyhelp_outline QHTNQHCVKNUPEI-ZAXAEIALSA-J SMILEShelp_outline C[C@H](CCC[C@H](C)C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C 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 A Identifier CHEBI:13193 Charge Formula R SMILEShelp_outline * 2D coordinates Mol file for the small molecule Search links Involved in 2,783 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 3-oxo-cholest-4,24-dien-26-oyl-CoA Identifier CHEBI:86414 Charge -4 Formula C48H70N7O18P3S InChIKeyhelp_outline GPXOWXUADRQDFI-MVJCTYHBSA-J SMILEShelp_outline C[C@H](CCC=C(C)C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline AH2 Identifier CHEBI:17499 Charge 0 Formula RH2 SMILEShelp_outline *([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 2,713 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:46688 | RHEA:46689 | RHEA:46690 | RHEA:46691 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Unraveling cholesterol catabolism in Mycobacterium tuberculosis: ChsE4-ChsE5 alpha2beta2 acyl-CoA dehydrogenase initiates beta-oxidation of 3-oxo-cholest-4-en-26-oyl CoA.
Yang M., Lu R., Guja K.E., Wipperman M.F., St Clair J.R., Bonds A.C., Garcia-Diaz M., Sampson N.S.
The metabolism of host cholesterol by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is an important factor for both its virulence and pathogenesis, although how and why cholesterol metabolism is required is not fully understood. <i>Mtb</i> uses a unique set of catabolic enzymes that are homologou ... >> More
The metabolism of host cholesterol by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is an important factor for both its virulence and pathogenesis, although how and why cholesterol metabolism is required is not fully understood. <i>Mtb</i> uses a unique set of catabolic enzymes that are homologous to those required for classical β-oxidation of fatty acids but are specific for steroid-derived substrates. Here, we identify and assign the substrate specificities of two of these enzymes, ChsE4-ChsE5 (Rv3504-Rv3505) and ChsE3 (Rv3573c), that carry out cholesterol side chain oxidation in <i>Mtb.</i> Steady-state assays demonstrate that ChsE4-ChsE5 preferentially catalyzes the oxidation of 3-oxo-cholest-4-en-26-oyl CoA in the first cycle of cholesterol side chain β-oxidation that ultimately yields propionyl-CoA, whereas ChsE3 specifically catalyzes the oxidation of 3-oxo-chol-4-en-24-oyl CoA in the second cycle of β-oxidation that generates acetyl-CoA. However, ChsE4-ChsE5 can catalyze the oxidation of 3-oxo-chol-4-en-24-oyl CoA as well as 3-oxo-4-pregnene-20-carboxyl-CoA. The functional redundancy of ChsE4-ChsE5 explains the in vivo phenotype of the <i>igr</i> knockout strain of <i>Mycobacterium tuberculosis</i>; the loss of ChsE1-ChsE2 can be compensated for by ChsE4-ChsE5 during the chronic phase of infection. The X-ray crystallographic structure of ChsE4-ChsE5 was determined to a resolution of 2.0 Å and represents the first high-resolution structure of a heterotetrameric acyl-CoA dehydrogenase (ACAD). Unlike typical homotetrameric ACADs that bind four flavin adenine dinucleotide (FAD) cofactors, ChsE4-ChsE5 binds one FAD at each dimer interface, resulting in only two substrate-binding sites rather than the classical four active sites. A comparison of the ChsE4-ChsE5 substrate-binding site to those of known mammalian ACADs reveals an enlarged binding cavity that accommodates steroid substrates and highlights novel prospects for designing inhibitors against the committed β-oxidation step in the first cycle of cholesterol side chain degradation by <i>Mtb</i>. << Less
ACS Infect. Dis. 1:110-125(2015) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.