The Crystal Structure And Inhibitors Of Chitinase CeChtl From Caenorhabditis Elegans

Plant-parasitic nematode infection was a worldwide threat to almost all major crops,causing damage to more than US$175 billion per year.However,there is a lack of efficient nematicide to control the agricultural damage caused by nematodes.However,the number of nematicides currently available in the market is small and reducing by prohibition for environmental impact or effectiveness losing by nematode resistant.During the egg-hatching process,the hydrolysis of eggshell chitin by nematode chitinase is crucial.Thus,inhibition of nematode chitinase by chemical agents to prevent nematode egg-hatching provides a practical approach to control plant-parasitic nematodes.However,lacking structural information of the chitinase for nematode egg-hatching hinders the target-based design of novel nematicides.Caenorhabditis elegans has been widely used as a model nematode for nematicide identification or mechanism study because of its advantages of easy culture,short lifecycle and independent on a host.Sequence analysis revealed that the chitinase CeChtl from C.elegans was highly similar to the parasitic nematode chitinases possessing a crucial function in egg-hatching.In this study,using CeChtl as the specific research object to catch a glimpse of the chitinases involving in nematode egg-hatching,we solved the first crystal structure of a nematode chitinase.Based on the crystal structure,we identified a novel nematode chitinase inhibitor which inhibited nematode egg-hatching.The crystal structure of the enzyme-inhibitor complex revealed the inhibition mechanism of this inhibitor.This work provided the information of target-structure and a novel lead-structure for the rational design of novel nematicides targeting the chitinase possessing a crucial function in egg-hatching.