Cloning and functional characterization of the geranylgeranyl diphosphate synthase(GGPPS)from Elizabethkingia meningoseptica sp.F2

2022 ◽  
Vol 189 ◽  
pp. 105986
Author(s):  
Qiang Yang ◽  
Zhiming Zheng ◽  
Genhai Zhao ◽  
Li Wang ◽  
Han Wang ◽  
...  
2013 ◽  
Vol 57 (12) ◽  
pp. 5969-5976 ◽  
Author(s):  
Peter D. Ziniel ◽  
Janish Desai ◽  
Cynthia L. Cass ◽  
Craig Gatto ◽  
Eric Oldfield ◽  
...  

ABSTRACTSchistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here thatSchistosoma mansonifarnesyl diphosphate synthase (SmFPPS) and geranylgeranyl diphosphate synthase (SmGGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinantSmFPPS andSmGGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. RecombinantSmFPPS was found to be a soluble 44.2-kDa protein, whileSmGGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. AgainstSmFPPS, several bisphosphonates had 50% inhibitory concentrations (IC50s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity againstSmGGPPS. Several lipophilic bisphosphonates were active againstex vivoadult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.


2015 ◽  
Vol 142 (4) ◽  
pp. 747-758 ◽  
Author(s):  
Shadi Rahimi ◽  
Yu-Jin Kim ◽  
Balusamy Sri Renuka Devi ◽  
Altanzul Khorolragchaa ◽  
Johan Sukweenadhi ◽  
...  

2013 ◽  
Vol 43 (10) ◽  
pp. 947-958 ◽  
Author(s):  
Aline Barbar ◽  
Manon Couture ◽  
Stephanie E. Sen ◽  
Catherine Béliveau ◽  
Audrey Nisole ◽  
...  

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