Structure and Function Studies of Insect Carboxylesterases [article]

Nicholas Fraser, University, The Australian National, University, The Australian National
2017
Insect carboxylesterases (CBEs) have great importance in insect biology and play a crucial role in the ever-increasing occurrence of insecticide resistance. This resistance to insecticides (e.g. organophosphates) leads to downstream effects on agriculture and to human health (through reduced crop production and the spread of insect-borne diseases). Structural and functional studies of insect CBEs are vital for combating insecticide resistance, finding new potential targets and in providing
more » ... d in providing insight into the evolution of new protein function. The work described in this thesis contributes to the overall understanding of the structure, function and evolution of insect CBEs. Chapter 1 is the introduction into the structure, function and evolution of insect CBEs. In particular, the classification of CBEs is discussed, as well, the current understanding of the role CBEs play in insect species. Chapter 2 describes the evolution of new oligomeric structure in the CBE αE7 from Lucilia cuprina and shows that higher order thermostable oligomers can be selected for during evolution. This work affirms the importance of oligomers in evolution to maintain or increase protein stability and demonstrates structure/activity trade-offs that are observed throughout enzyme evolution. Chapter 3 describes structural studies into the CBE esterase-6 (EST6) from Drosophila melanogaster - a CBE that has shown to be important for the reproductive success of Drosophila species. The enzyme has a unique active site entry for insect CBEs, which results in a narrow and shortened active site. Docking simulations in combination with kinetic analyses show that the enzyme is a probable odorant-degrading enzyme. It also indicates that EST6 does not directly interact with the sex pheromone 11-cis vaccenyl acetate (cVA), which contradicts the previously held belief that it is the main substrate of the enzyme. The evolution of CBEs involved in insecticide resistance in several species is discussed in Chapter 4. α-esterase orthologs from different dipteran [...]
doi:10.25911/5d70f13448567 fatcat:vun24uikonfjnnpq4lf7uin2xe