Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic
Citrus huanglongbing (HLB) is a destructive disease that causes significant damage to many citrus producing areas worldwide. To date, no strategy against this disease has been established. Inosine 5′-monophosphate dehydrogenase (IMPDH) plays crucial roles in the de novo synthesis of guanine nucleoti...
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/10/2313 |
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| author | Jing Nan Shaoran Zhang Ping Zhan Ling Jiang |
| author_facet | Jing Nan Shaoran Zhang Ping Zhan Ling Jiang |
| author_sort | Jing Nan |
| collection | DOAJ |
| description | Citrus huanglongbing (HLB) is a destructive disease that causes significant damage to many citrus producing areas worldwide. To date, no strategy against this disease has been established. Inosine 5′-monophosphate dehydrogenase (IMPDH) plays crucial roles in the de novo synthesis of guanine nucleotides. This enzyme is used as a potential target to treat bacterial infection. In this study, the crystal structure of a deletion mutant of <i>C</i>Las IMPDHΔ98-201 in the apo form was determined. Eight known bioactive compounds were used as ligands for molecular docking. The results showed that bronopol and disulfiram bound to <i>C</i>Las IMPDHΔ98-201 with high affinity. These compounds were tested for their inhibition against <i>C</i>Las IMPDHΔ98-201 activity. Bronopol and disulfiram showed high inhibition at nanomolar concentrations, and bronopol was found to be the most potent molecule (K<sub>i</sub> = 234 nM). The K<sub>i</sub> value of disulfiram was 616 nM. These results suggest that bronopol and disulfiram can be considered potential candidate agents for the development of <i>C</i>Las inhibitors. |
| first_indexed | 2024-03-10T19:50:05Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:50:05Z |
| publishDate | 2020-05-01 |
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| series | Molecules |
| spelling | doaj.art-ec7470c18f59467ea1bf3f37f3f92f772023-11-20T00:29:58ZengMDPI AGMolecules1420-30492020-05-012510231310.3390/molecules25102313Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme KineticJing Nan0Shaoran Zhang1Ping Zhan2Ling Jiang3College of Horticulture and Forestry, Key Laboratory of Horticultural Plant Biology of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Horticulture and Forestry, Key Laboratory of Horticultural Plant Biology of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Horticulture and Forestry, Key Laboratory of Horticultural Plant Biology of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, ChinaCitrus huanglongbing (HLB) is a destructive disease that causes significant damage to many citrus producing areas worldwide. To date, no strategy against this disease has been established. Inosine 5′-monophosphate dehydrogenase (IMPDH) plays crucial roles in the de novo synthesis of guanine nucleotides. This enzyme is used as a potential target to treat bacterial infection. In this study, the crystal structure of a deletion mutant of <i>C</i>Las IMPDHΔ98-201 in the apo form was determined. Eight known bioactive compounds were used as ligands for molecular docking. The results showed that bronopol and disulfiram bound to <i>C</i>Las IMPDHΔ98-201 with high affinity. These compounds were tested for their inhibition against <i>C</i>Las IMPDHΔ98-201 activity. Bronopol and disulfiram showed high inhibition at nanomolar concentrations, and bronopol was found to be the most potent molecule (K<sub>i</sub> = 234 nM). The K<sub>i</sub> value of disulfiram was 616 nM. These results suggest that bronopol and disulfiram can be considered potential candidate agents for the development of <i>C</i>Las inhibitors.https://www.mdpi.com/1420-3049/25/10/2313<i>Candidatus</i> Liberibacter asiaticusInosine 5′-monophosphate dehydrogenasecrystalmolecular dockingenzyme activityantibacterial compound |
| spellingShingle | Jing Nan Shaoran Zhang Ping Zhan Ling Jiang Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic Molecules <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-monophosphate dehydrogenase crystal molecular docking enzyme activity antibacterial compound |
| title | Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic |
| title_full | Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic |
| title_fullStr | Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic |
| title_full_unstemmed | Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic |
| title_short | Evaluation of Bronopol and Disulfiram as Potential <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic |
| title_sort | evaluation of bronopol and disulfiram as potential i candidatus i liberibacter asiaticus inosine 5 monophosphate dehydrogenase inhibitors by using molecular docking and enzyme kinetic |
| topic | <i>Candidatus</i> Liberibacter asiaticus Inosine 5′-monophosphate dehydrogenase crystal molecular docking enzyme activity antibacterial compound |
| url | https://www.mdpi.com/1420-3049/25/10/2313 |
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