Enzymes
| UniProtKB help_outline | 2 proteins |
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- Name help_outline (22E)-3-oxochola-4,22-dien-24-oyl-CoA Identifier CHEBI:136759 Charge -4 Formula C45H64N7O18P3S InChIKeyhelp_outline KECDKXTVBMMQTC-FZQSAGNESA-J SMILEShelp_outline C(/C=C/[C@]([C@@]1([C@]2(CC[C@@]3([C@]4(CCC(C=C4CC[C@]3([C@@]2(CC1)[H])[H])=O)C)[H])C)[H])(C)[H])(=O)SCCNC(CCNC(=O)[C@@H](C(COP(OP(OC[C@H]5O[C@@H](N6C7=C(C(=NC=N7)N)N=C6)[C@@H]([C@@H]5OP([O-])([O-])=O)O)(=O)[O-])(=O)[O-])(C)C)O)=O 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 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 (22R)-hydroxy-3-oxo-chol-4-ene-24-oyl-CoA Identifier CHEBI:192383 Charge -4 Formula C45H66N7O19P3S InChIKeyhelp_outline PWKWOPLMMQRHSP-BIYRDJFFSA-J SMILEShelp_outline C(C[C@H]([C@]([C@@]1([C@]2(CC[C@@]3([C@]4(CCC(C=C4CC[C@]3([C@@]2(CC1)[H])[H])=O)C)[H])C)[H])(C)[H])O)(=O)SCCNC(CCNC(=O)[C@@H](C(COP(OP(OC[C@H]5O[C@@H](N6C7=C(C(=NC=N7)N)N=C6)[C@@H]([C@@H]5OP([O-])([O-])=O)O)(=O)[O-])(=O)[O-])(C)C)O)=O 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
Cross-references
| RHEA:72575 | RHEA:72576 | RHEA:72577 | RHEA:72578 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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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.
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Enzymatic beta-Oxidation of the Cholesterol Side Chain in Mycobacterium tuberculosis Bifurcates Stereospecifically at Hydration of 3-Oxo-cholest-4,22-dien-24-oyl-CoA.
Yuan T., Werman J.M., Yin X., Yang M., Garcia-Diaz M., Sampson N.S.
The unique ability of <i>Mycobacterium tuberculosis</i> (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development. Herein, we identify and characterize two genes fro ... >> More
The unique ability of <i>Mycobacterium tuberculosis</i> (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development. Herein, we identify and characterize two genes from the Cho-region (genomic locus responsible for cholesterol catabolism) of the Mtb genome, <i>chsH3</i> (Rv3538) and <i>chsB1</i> (Rv3502c). Their protein products catalyze two sequential stereospecific hydration and dehydrogenation steps in the β-oxidation of the cholesterol side chain. ChsH3 favors the 22<i>S</i> hydration of 3-oxo-cholest-4,22-dien-24-oyl-CoA in contrast to the previously reported EchA19 (Rv3516), which catalyzes formation of the (22<i>R</i>)-hydroxy-3-oxo-cholest-4-en-24-oyl-CoA from the same enoyl-CoA substrate. ChsB1 is stereospecific and catalyzes dehydrogenation of the ChsH3 product but not the EchA19 product. The X-ray crystallographic structure of the ChsB1 apo-protein was determined at a resolution of 2.03 Å, and the holo-enzyme with bound NAD<sup>+</sup> cofactor was determined at a resolution of 2.21 Å. The homodimeric structure is representative of a classical NAD<sup>+</sup>-utilizing short-chain type alcohol dehydrogenase/reductase, including a Rossmann-fold motif, but exhibits a unique substrate binding site architecture that is of greater length and width than its homologous counterparts, likely to accommodate the bulky steroid substrate. Intriguingly, Mtb utilizes hydratases from the MaoC-like family in sterol side-chain catabolism in contrast to fatty acid β-oxidation in other species that utilize the evolutionarily distinct crotonase family of hydratases. << Less
ACS Infect. Dis. 7:1739-1751(2021) [PubMed] [EuropePMC]
This publication is cited by 4 other entries.