Enzymes
| UniProtKB help_outline | 11,493 proteins |
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| GO Molecular Function help_outline |
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Reaction participants Show >> << Hide
- Name help_outline acetyl-CoA Identifier CHEBI:57288 (Beilstein: 8468140) help_outline Charge -4 Formula C23H34N7O17P3S InChIKeyhelp_outline ZSLZBFCDCINBPY-ZSJPKINUSA-J SMILEShelp_outline 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 321 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline an acyl-CoA Identifier CHEBI:58342 Charge -4 Formula C22H31N7O17P3SR SMILEShelp_outline CC(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](O)C(=O)NCCC(=O)NCCSC([*])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,973 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline a 3-oxoacyl-CoA Identifier CHEBI:90726 Charge -4 Formula C24H33N7O18P3SR SMILEShelp_outline [C@@H]1(N2C3=C(C(=NC=N3)N)N=C2)O[C@H](COP(OP(OCC([C@H](C(NCCC(NCCSC(=O)CC(=O)*)=O)=O)O)(C)C)(=O)[O-])(=O)[O-])[C@H]([C@H]1O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 153 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CoA Identifier CHEBI:57287 (Beilstein: 11604429) help_outline Charge -4 Formula C21H32N7O16P3S InChIKeyhelp_outline RGJOEKWQDUBAIZ-IBOSZNHHSA-J SMILEShelp_outline CC(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](O)C(=O)NCCC(=O)NCCS 2D coordinates Mol file for the small molecule Search links Involved in 1,468 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:21564 | RHEA:21565 | RHEA:21566 | RHEA:21567 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Related reactions help_outline
Specific form(s) of this reaction
- RHEA:67224
- RHEA:46312
- RHEA:35279
- RHEA:34799
- RHEA:31203
- RHEA:31183
- RHEA:31111
- RHEA:31091
- RHEA:31087
- RHEA:21036
- RHEA:19481
- RHEA:18161
Publications
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A thiolase of Mycobacterium tuberculosis is required for virulence and production of androstenedione and androstadienedione from cholesterol.
Nesbitt N.M., Yang X., Fontan P., Kolesnikova I., Smith I., Sampson N.S., Dubnau E.
Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that shifts to a lipid-based metabolism in the host. Moreover, metabolism of the host lipid cholesterol plays an important role in M. tuberculosis infection. We used transcriptional profiling to identify ... >> More
Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that shifts to a lipid-based metabolism in the host. Moreover, metabolism of the host lipid cholesterol plays an important role in M. tuberculosis infection. We used transcriptional profiling to identify genes transcriptionally regulated by cholesterol and KstR (Rv3574), a TetR-like repressor. The fadA5 (Rv3546) gene, annotated as a lipid-metabolizing thiolase, the expression of which is upregulated by cholesterol and repressed by KstR, was deleted in M. tuberculosis H37Rv. We demonstrated that fadA5 is required for utilization of cholesterol as a sole carbon source in vitro and for full virulence of M. tuberculosis in the chronic stage of mouse lung infection. Cholesterol is not toxic to the fadA5 mutant strain, and, therefore, toxicity does not account for its attenuation. We show that the wild-type strain, H37Rv, metabolizes cholesterol to androst-4-ene-3,17-dione (AD) and androsta-1,4-diene-3,17-dione (ADD) and exports these metabolites into the medium, whereas the fadA5 mutant strain is defective for this activity. We demonstrate that FadA5 catalyzes the thiolysis of acetoacetyl-coenzyme A (CoA). This catalytic activity is consistent with a beta-ketoacyl-CoA thiolase function in cholesterol beta-oxidation that is required for the production of androsterones. We conclude that the attenuated phenotype of the fadA5 mutant is a consequence of disrupted cholesterol metabolism that is essential only in the persistent stage of M. tuberculosis infection and may be caused by the inability to produce AD/ADD from cholesterol. << Less
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Enzymatic breakdown and synthesis of acetoacetate.
STERN J.R., COON M.J., DEL CAMPILLO A.
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FadA5 a thiolase from Mycobacterium tuberculosis: a steroid-binding pocket reveals the potential for drug development against tuberculosis.
Schaefer C.M., Lu R., Nesbitt N.M., Schiebel J., Sampson N.S., Kisker C.
With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new antitubercular drugs is apparent due to the increasing number of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import ... >> More
With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new antitubercular drugs is apparent due to the increasing number of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import and metabolism have recently been discovered as potent targets against TB. FadA5, a thiolase from Mtb, is catalyzing the last step of the β-oxidation reaction of the cholesterol side-chain degradation under release of critical metabolites and was shown to be of importance during the chronic stage of TB infections. To gain structural and mechanistic insight on FadA5, we characterized the enzyme in different stages of the cleavage reaction and with a steroid bound to the binding pocket. Structural comparisons to human thiolases revealed that it should be possible to target FadA5 specifically, and the steroid-bound structure provides a solid basis for the development of inhibitors against FadA5. << Less
Structure 23:21-33(2015) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Studies on the fatty acid oxidizing system of animal tissues. VII. The beta-ketoacyl coenzyme A cleavage enzyme.
GOLDMAN D.S.
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Antifungal activity of Saccharomyces cerevisiae peroxisomal 3-ketoacyl-CoA thiolase.
Lee J.R., Kim S.Y., Chae H.B., Jung J.H., Lee S.Y.
Peroxisomes play an important role in cellular defense systems and generate secondary messengers for cellular communication. Saccharomyces cerevisiae containing oleate-induced peroxisomes were subjected to buffer-soluble extraction and two chromatographic procedures, and a protein with antifungal ... >> More
Peroxisomes play an important role in cellular defense systems and generate secondary messengers for cellular communication. Saccharomyces cerevisiae containing oleate-induced peroxisomes were subjected to buffer-soluble extraction and two chromatographic procedures, and a protein with antifungal activity was isolated. The results of MALDI-TOF analysis identified the isolated protein as peroxisomal 3-ketoacyl-CoA thiolase (ScFox3). Purified yeast ScFox3 exhibited thiolase activity that catalyzed the thiolytic cleavage of 3-ketoacyl-CoA to acetyl-CoA and acyl-CoA. ScFox3 protein inhibited various pathogenic fungal strains, with the exception of Aspergillus flavus. Using ScFox3-GFP and PTS2 signal-truncated ScFox3M-GFP, we showed that only ScFox3-GFP, with an intact PTS2 peroxisome signal sequence, was able to translocate into peroxisomes. Yeast ScFox3 is a natural antifungal agent found in peroxisomes. << Less
BMB Rep 42:281-285(2009) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.