The Rational Design And Theoretical Study Based On FBPase And SBPase Inhibitors

Photosynthesis is an important physiological and biochemical process of green plants, and herbicides of inhibiting photosynthesis are widely studies in herbicide research. The development of computer-aided drug design, high-throughput virtual screening and enzyme assay technology, can greatly accelerate the period of novel pesticides research and reduce the cost of research. In this thesis, we use these technologies to study two very significant catalytic hydrolysis enzymes for Calvin cycle of green plants, fructose-1, 6-biphosphatase (FBPase) and sedoheptulose-1, 7 -bisphosphatase (SBPase). The levels of fructose-1, 6-bisphosphatase (FBPase) and sedoheptulose-1, 7 -bisphosphatase (SBPase) are extremely low compared with those of other enzymes in the Calvin cycle of plants. Transgenic plants with a small decrease in the activities of FBPase or SBPase exhibits a reduction in photosynthetic capacity, indicating that the reduction in photosynthesis results from a reduction in the regenerative capacity of the Calvin cycle. SBPase is a potential target for herbicide research because of its enormous significance for photosynthesis and only existing in high plants. We look into the mechanism for the hydrolysis of FBPase and SBPase in detail and rationally design inhibitors by computer-aided drug design (CADD) methods.Cyanobacterial cells contain a unique enzyme, fructose-1,6-bisphosphatase /sedoheptulose-1,7-bisphosphatase (FBPase/SBPase), which can hydrolyze both FBP and SBP with almost equal specific activities. We predict the 3D structure of cyan bacteria by homology modeling for virtual screening in SPECS database. A representative set of 30 candidates based on scoring functions are sorted out for in vitro tests. Four out of 30 candidates with better inhibitory activity are selected for further structural optimization.Based on the homology between SBPase and FBPase, predictive model of Arabidopsis thaliana SBPase is established by homology modeling. 25 candidates are selected for the enzyme assay after molecular docking in SPECS database. Right now the enzyme assay is in progress.