Enzymes
| UniProtKB help_outline | 2 proteins |
Reaction participants Show >> << Hide
- Name help_outline (2E)-octenoyl-CoA Identifier CHEBI:62242 Charge -4 Formula C29H44N7O17P3S InChIKeyhelp_outline CPSDNAXXKWVYIY-NTLMCJQISA-J SMILEShelp_outline CCCCC\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 2D coordinates Mol file for the small molecule Search links Involved in 10 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 3-hydroxyoctanoyl-CoA Identifier CHEBI:86040 Charge -4 Formula C29H46N7O18P3S InChIKeyhelp_outline ATVGTMKWKDUCMS-UGRYODIPSA-J SMILEShelp_outline CCCCCC(O)CC(=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 2D coordinates Mol file for the small molecule Search links Involved in 6 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:46348 | RHEA:46349 | RHEA:46350 | RHEA:46351 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
|
Related reactions help_outline
Specific form(s) of this reaction
More general form(s) of this reaction
Publications
-
Post-translational Succinylation of Mycobacterium tuberculosis Enoyl-CoA Hydratase EchA19 Slows Catalytic Hydration of Cholesterol Catabolite 3-Oxo-chol-4,22-diene-24-oyl-CoA.
Bonds A.C., Yuan T., Werman J.M., Jang J., Lu R., Nesbitt N.M., Garcia-Diaz M., Sampson N.S.
Cholesterol is a major carbon source for <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) during infection, and cholesterol utilization plays a significant role in persistence and virulence within host macrophages. Elucidating the mechanism by which cholesterol is degraded may permit the identificat ... >> More
Cholesterol is a major carbon source for <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) during infection, and cholesterol utilization plays a significant role in persistence and virulence within host macrophages. Elucidating the mechanism by which cholesterol is degraded may permit the identification of new therapeutic targets. Here, we characterized EchA19 (Rv3516), an enoyl-CoA hydratase involved in cholesterol side-chain catabolism. Steady-state kinetics assays demonstrated that EchA19 preferentially hydrates cholesterol enoyl-CoA metabolite 3-oxo-chol-4,22-diene-24-oyl-CoA, an intermediate of side-chain β-oxidation. In addition, succinyl-CoA, a downstream catabolite of propionyl-CoA that forms during cholesterol degradation, covalently modifies targeted mycobacterial proteins, including EchA19. Inspection of a 1.9 Å resolution X-ray crystallography structure of <i>Mtb</i> EchA19 suggests that succinylation of Lys132 and Lys139 may perturb enzymatic activity by modifying the entrance to the substrate binding site. Treatment of EchA19 with succinyl-CoA revealed that these two residues are hotspots for succinylation. Replacement of these specific lysine residues with negatively charged glutamate reduced the rate of catalytic hydration of 3-oxo-chol-4,22-diene-24-oyl-CoA by EchA19, as does succinylation of EchA19. Our findings suggest that succinylation is a negative feedback regulator of cholesterol metabolism, thereby adding another layer of complexity to <i>Mtb</i> physiology in the host. These regulatory pathways are potential noncatabolic targets for antimicrobial drugs. << Less
ACS Infect. Dis. 6:2214-2224(2020) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
-
A distinct MaoC-like enoyl-CoA hydratase architecture mediates cholesterol catabolism in Mycobacterium tuberculosis.
Yang M., Guja K.E., Thomas S.T., Garcia-Diaz M., Sampson N.S.
The Mycobacterium tuberculosis (Mtb) igr operon plays an essential role in Mtb cholesterol metabolism, which is critical for pathogenesis during the latent stage of Mtb infection. Here we report the first structure of a heterotetrameric MaoC-like enoyl-CoA hydratase, ChsH1-ChsH2, which is encoded ... >> More
The Mycobacterium tuberculosis (Mtb) igr operon plays an essential role in Mtb cholesterol metabolism, which is critical for pathogenesis during the latent stage of Mtb infection. Here we report the first structure of a heterotetrameric MaoC-like enoyl-CoA hydratase, ChsH1-ChsH2, which is encoded by two adjacent genes from the igr operon. We demonstrate that ChsH1-ChsH2 catalyzes the hydration of a steroid enoyl-CoA, 3-oxo-4,17-pregnadiene-20-carboxyl-CoA, in the modified β-oxidation pathway for cholesterol side chain degradation. The ligand-bound and apoenzyme structures of ChsH1-ChsH2(N) reveal an unusual, modified hot-dog fold with a severely truncated central α-helix that creates an expanded binding site to accommodate the bulkier steroid ring system. The structures show quaternary structure shifts that accommodate the four rings of the steroid substrate and offer an explanation for why the unusual heterotetrameric assembly is utilized for hydration of this steroid. The unique αβ heterodimer architecture utilized by ChsH1-ChsH2 to bind its distinctive substrate highlights an opportunity for the development of new antimycobacterial drugs that target a pathway specific to Mtb. << Less
ACS Chem. Biol. 9:2632-2645(2014) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.