Structural highlights
Function[C6XG59_LIBAP] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964] Publication Abstract from PubMedCitrus 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 CLas IMPDHDelta98-201 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 IMPDHDelta98-201 with high affinity. These compounds were tested for their inhibition against CLas IMPDHDelta98-201 activity. Bronopol and disulfiram 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. Evaluation of Bronopol and Disulfiram as Potential Candidatus Liberibacter asiaticus Inosine 5'-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic.,Nan J, Zhang S, Zhan P, Jiang L Molecules. 2020 May 14;25(10). pii: molecules25102313. doi:, 10.3390/molecules25102313. PMID:32423116[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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