Discovery of Novel GMPS Inhibitors of Candidatus Liberibacter Asiaticus by Structure Based Design and Enzyme Kinetic

Biology

Ling Jiang¹  Ping Zhan¹  Jing Nan¹  Shaoran Zhang² 

[1] Ministry of Education Key Laboratory of Plant Biology, Huazhong Agricultural University, Wuhan 430070, China;State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China;

关键词: Candidatus Liberibacter asiaticus;    guanosine 5′-monophosphate synthetase;    virtual screening;    molecular docking;    enzyme activity;   

DOI  :  10.3390/biology10070594

来源: DOAJ

【 摘 要 】

Citrus production is facing an unprecedented problem because of huanglongbing (HLB) disease. Presently, no effective HLB-easing method is available when citrus becomes infected. Guanosine 5′-monophosphate synthetase (GMPS) is a key protein in the de novo synthesis of guanine nucleotides. GMPS is used as an attractive target for developing agents that are effective against the patogen infection. In this research, homology modeling, structure-based virtual screening, and molecular docking were used to discover the new inhibitors against CLas GMPS. Enzyme assay showed that folic acid and AZD1152 showed high inhibition at micromole concentrations, with AZD1152 being the most potent molecule. The inhibition constant (K_i) value of folic acid and AZD1152 was 51.98 µM and 4.05 µM, respectively. These results suggested that folic acid and AZD1152 could be considered as promising candidates for the development of CLas agents.

【 授权许可】

Unknown