6KCF

Structure of Inosine 5'-monophosphate Dehydrogenase from Candidatus Liberibacter asiaticus str. psy62

Summary for 6KCF

• Entry DOI: 10.2210/pdb6kcf/pdb
• Descriptor: Inosine-5'-monophosphate dehydrogenase (2 entities in total)
• Functional Keywords: inosine 5'-monophosphate dehydrogenase, oxidoreductase
• Biological source: Liberibacter asiaticus (strain psy62); More
• Total number of polymer chains: 4
• Total formula weight: 164239.86

Authors

Nan, J.,Zhang, S.R.,Jiang, L. (deposition date: 2019-06-28, release date: 2019-08-28, Last modification date: 2024-03-27)

Primary citation

Nan, J.,Zhang, S.,Zhan, P.,Jiang, L.
Evaluation of Bronopol and Disulfiram as Potential Candidatus Liberibacter asiaticus Inosine 5'-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic.
Molecules, 25:-, 2020

PubMed Abstract: 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 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 Las IMPDHΔ98-201 with high affinity. These compounds were tested for their inhibition against Las IMPDHΔ98-201 activity. Bronopol and disulfiram showed high inhibition at nanomolar concentrations, and bronopol was found to be the most potent molecule (K = 234 nM). The K value of disulfiram was 616 nM. These results suggest that bronopol and disulfiram can be considered potential candidate agents for the development of Las inhibitors.

PubMed: 32423116
DOI: 10.3390/molecules25102313

Experimental method

X-RAY DIFFRACTION (2.55 Å)