What makes an enzyme a good insecticide sponge?

Hopkins, D. H., Fraser, N. J., Mabbitt, P. D., Carr, P. D., Oakeshott, J. G., & Jackson, C. J. (2017). The structure of an insecticide sequestering carboxylesterase from the disease vector Culex quinquefasciatus: what makes an enzyme a good insecticide sponge? Biochemistry, acs.biochem.7b00774. https://doi.org/10.1021/acs.biochem.7b00774

A molecular understanding of pesticide sequestration by insect carboxylesterases could guide the design of inhibitors to help circumvent carboxylesterase-mediated metabolic resistance to organophosphate and carbamate insecticides in insect disease vectors, such as the mosquito.

In a recently accepted paper from our group, entitled “The structure of an insecticide sequestering carboxylesterase from the disease vector Culex quinquefasciatus: what makes an enzyme a good insecticide sponge?”, we present the first structure of Cqestβ2, a carboxylesterase involved in insecticide sequestration in Culex quinquefasciatus, and assess its role in insecticide resistance.

Congratulations to Davis and all those involved in the preparation of this paper which has recently been accepted to Biochemistry. 







New Honours Student!

We welcome Tiffany Chau to the group! Tiffany is starting her Honours year and will be co-supervised by Professor Thomas Huber. She will be continuing the work done by Jules Kirk on EF-Tu (elongation factor thermo unstable), a prokaryotic elongation factor responsible for catalysing the binding of an aminoacyl-tRNA to the ribosome. Welcome Tiffany!

Hafna awarded the Vince Massey Award!


Hafna recently attended the 19th International Symposium on Flavins and Flavoproteins held in Groningen in the Netherlands. This is the largest and most specialised conference held in the field of flavin research and has been held triennially for the last 60 years. Hafna presented the work she did during her PhD on F420 binding proteins among the flavin/deazaflavin dependent oxidoreductases, and was presented with the Vince Massey Award for young investigators who have shown an outstanding contribution to the field of flavins and flavoenzymes. Top work Hafna!!

You can read about this work here:


Overcoming insecticide resistance through computational inhibitor design

Check out Galen’s latest work on the computational design of reversible covalent picomolar inhibitors of carboxylesterase αE7 – helping to overcome insecticide resistance! The manuscript ‘Overcoming insecticide resistance through computational inhibitor design’ is now available as a preprint on bioRxiv! In this work, done in collaboration with the London lab at the Weizmann Institute of Science, we use covalent computational design to produce nano/pico-molar boronic acid inhibitors of the carboxylesterase αE7 from the agricultural pest Lucilia cuprina, as well as a common Gly137Asp αE7 mutant that confers OP resistance. These inhibitors, with no intrinsic apparent toxicity, act synergistically with the OPs diazinon and malathion to reduce the amount of OP required to kill L. cuprina by up to 16-fold, and abolish resistance. These compounds represent a solution to insecticide resistance. Shoo fly!


New Publication

Nick, Paul and Colin contributed to the recently accepted paper “The Synthesis of Certain Derivatives and Analogues of (–)- and (+)-Galanthamine and an Assessment of their Capacities to Inhibit Acetylcholine Esterase” in The Journal of Organic Chemistry. This work, done in collaboration with the Banwell group at ANU, describes the syntheses of certain di- and mono-oxygenated derivatives and analogues of the alkaloid galanthamine. In contrast to results from docking studies, we show that none of these compounds strongly bind to acetylcholine esterase.



New Publication

Congratulations to Paul, Galen and Colin for their work on the paper Total Syntheses of the Amaryllidaceae Alkaloids Zephycandidine III and Lycosinine A and Their Evaluation as Inhibitors of Acetylcholinesterase”, which was recently accepted to the European Journal of Organic Chemistry. This collaboration with the Banwell Group (ANU) describes the total synthesis of the amaryllidaceae alkaloids Zephycandidine III and Lycosinine A. Contrary to an earlier study, these compounds are shown to be poor inhibitors of acetylcholinesterase. 

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