Advance Publications: Research Papers:
Analysis and application of the SRBSDV P91 octamer crystal structure for the target of αamino phosphonate derivatives
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Yan Ding1, Xiangyang Li1, Kai Chen1, Guoping Zhang1, Liangzhi Luo1, Deyu Hu1 and Baoan Song1
1State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, PR China
Correspondence to:
Baoan Song, email: [email protected]
Xiangyang Li, email: [email protected]
Keywords: targets; SRBSDV P9-1; octamers; bind to; α-amino phosphonate derivatives
Received: October 17, 2017 Accepted: December 05, 2017 Published: January 13, 2018
ABSTRACT
Southern rice black-streaked dwarf virus (SRBSDV) P9-1 octameric protein accumulates viroplasms in SRBSDV-infected plant and insect cells, our previous studies found α-amino phosphonate drug—dufulin had a micromole affinity with SRBSDV P9-1. Now we focus our studies on the SRBSDV P9-1 crystal structure and use it as the target for α-amino phosphonate derivatives. The structure of the SRBSDV P9-1 cylindrical octamer was determined to a 2.2 Å resolution using X-ray crystallography, this structure was composed of nine α-helices, nine β-sheets and a series of interconnecting loops. The structures of all eight subunits were nearly identical, except for some differences in the β-sheet core. There were six different sites (R20K, V109D, F164T, V123L, C124L and V128T) present between the SRBSDV P9-1 and the previously reported RBSDV P9-1 crystal structure. Fluorescence titration, isothermal calorimetry and microscale thermophoresis experiments showed that α-amino phosphonate derivatives GUFCC-013 and GUFCC-023 bound to SRBSDV P9-1 with micromole binding affinities. These results will provide important help for the further improvement of the lead compound and develop the potential anti-SRBSDV drugs.