Evaluation of Bronopol and Disulfifiram as Potential Candidatus Liberibacter asiaticus Inosine 5‘-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic
Evaluation of Bronopol and Disulfifiram as Potential Candidatus Liberibacter asiaticus Inosine 5‘-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic
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DOI：
10.3390/molecules25102313
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ling Jiang
中科院分区：
文献类型：
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作者：
Jing Nan;Shaoran Zhang;Ping Zhan;Ling Jiang
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 50 -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 CLas IMPDH∆98-201 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 CLas IMPDH∆98-201 with high affinity. These compounds were tested for their inhibition against CLas IMPDH∆98-201 activity. Bronopol and isulfiram showed high inhibition at nanomolar concentrations, and bronopol was found to be the most potent molecule (Ki = 234 nM). The Ki value of disulfiram was 616 nM. These results suggest that bronopol and disulfiram can be considered potential candidate agents for the development of CLas inhibitors.
