Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives
The genome of the human intracellular pathogen <i>Mycobacterium tuberculosis</i> encodes an unusually large number of epoxide hydrolases, which are thought to be involved in lipid metabolism and detoxification reactions needed to endure the hostile environment of host macrophages. These...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/6/2884 |
| _version_ | 1797541552043589632 |
|---|---|
| author | Jan Madacki Martin Kopál Mary Jackson Jana Korduláková |
| author_facet | Jan Madacki Martin Kopál Mary Jackson Jana Korduláková |
| author_sort | Jan Madacki |
| collection | DOAJ |
| description | The genome of the human intracellular pathogen <i>Mycobacterium tuberculosis</i> encodes an unusually large number of epoxide hydrolases, which are thought to be involved in lipid metabolism and detoxification reactions needed to endure the hostile environment of host macrophages. These enzymes therefore represent suitable targets for compounds such as urea derivatives, which are known inhibitors of soluble epoxide hydrolases. In this work, we studied in vitro the effect of the thiourea drug isoxyl on six epoxide hydrolases of <i>M. tuberculosis</i> using a fatty acid substrate. We show that one of the proteins inhibited by isoxyl is EphD, an enzyme involved in the metabolism of mycolic acids, key components of the mycobacterial cell wall. By analyzing mycolic acid profiles, we demonstrate the inhibition of EphD epoxide hydrolase activity by isoxyl and two other urea-based inhibitors, thiacetazone and AU1235, inside the mycobacterial cell. |
| first_indexed | 2024-03-10T13:17:34Z |
| format | Article |
| id | doaj.art-986ffa6739ba4a0ba3b9c553f989ee32 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:17:34Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-986ffa6739ba4a0ba3b9c553f989ee322023-11-21T10:15:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226288410.3390/ijms22062884Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea DerivativesJan Madacki0Martin Kopál1Mary Jackson2Jana Korduláková3Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 842 15 Bratislava, SlovakiaDepartment of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 842 15 Bratislava, SlovakiaMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USADepartment of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 842 15 Bratislava, SlovakiaThe genome of the human intracellular pathogen <i>Mycobacterium tuberculosis</i> encodes an unusually large number of epoxide hydrolases, which are thought to be involved in lipid metabolism and detoxification reactions needed to endure the hostile environment of host macrophages. These enzymes therefore represent suitable targets for compounds such as urea derivatives, which are known inhibitors of soluble epoxide hydrolases. In this work, we studied in vitro the effect of the thiourea drug isoxyl on six epoxide hydrolases of <i>M. tuberculosis</i> using a fatty acid substrate. We show that one of the proteins inhibited by isoxyl is EphD, an enzyme involved in the metabolism of mycolic acids, key components of the mycobacterial cell wall. By analyzing mycolic acid profiles, we demonstrate the inhibition of EphD epoxide hydrolase activity by isoxyl and two other urea-based inhibitors, thiacetazone and AU1235, inside the mycobacterial cell.https://www.mdpi.com/1422-0067/22/6/2884mycobacteriumepoxide hydrolaseisoxylthiacetazoneAU1235mycolic acids |
| spellingShingle | Jan Madacki Martin Kopál Mary Jackson Jana Korduláková Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives International Journal of Molecular Sciences mycobacterium epoxide hydrolase isoxyl thiacetazone AU1235 mycolic acids |
| title | Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives |
| title_full | Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives |
| title_fullStr | Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives |
| title_full_unstemmed | Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives |
| title_short | Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives |
| title_sort | mycobacterial epoxide hydrolase ephd is inhibited by urea and thiourea derivatives |
| topic | mycobacterium epoxide hydrolase isoxyl thiacetazone AU1235 mycolic acids |
| url | https://www.mdpi.com/1422-0067/22/6/2884 |
| work_keys_str_mv | AT janmadacki mycobacterialepoxidehydrolaseephdisinhibitedbyureaandthioureaderivatives AT martinkopal mycobacterialepoxidehydrolaseephdisinhibitedbyureaandthioureaderivatives AT maryjackson mycobacterialepoxidehydrolaseephdisinhibitedbyureaandthioureaderivatives AT janakordulakova mycobacterialepoxidehydrolaseephdisinhibitedbyureaandthioureaderivatives |