Structure and function of an insect α-carboxylesterase (αEsterase7) associated with insecticide resistance

Proceedings of the National Academy of Sciences of the United States of America
Colin J JacksonJohn G Oakeshott

Abstract

Insect carboxylesterases from the αEsterase gene cluster, such as αE7 (also known as E3) from the Australian sheep blowfly Lucilia cuprina (LcαE7), play an important physiological role in lipid metabolism and are implicated in the detoxification of organophosphate (OP) insecticides. Despite the importance of OPs to agriculture and the spread of insect-borne diseases, the molecular basis for the ability of α-carboxylesterases to confer OP resistance to insects is poorly understood. In this work, we used laboratory evolution to increase the thermal stability of LcαE7, allowing its overexpression in Escherichia coli and structure determination. The crystal structure reveals a canonical α/β-hydrolase fold that is very similar to the primary target of OPs (acetylcholinesterase) and a unique N-terminal α-helix that serves as a membrane anchor. Soaking of LcαE7 crystals in OPs led to the capture of a crystallographic snapshot of LcαE7 in its phosphorylated state, which allowed comparison with acetylcholinesterase and rationalization of its ability to protect insects against the effects of OPs. Finally, inspection of the active site of LcαE7 reveals an asymmetric and hydrophobic substrate binding cavity that is well-suited to fatty aci...Continue Reading

References

Jan 1, 1993·Pharmacology & Therapeutics·T C Marrs
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·R D NewcombJ G Oakeshott
Apr 5, 2001·Journal of Applied Toxicology : JAT·B Ballantyne, T J Cawley
May 30, 2001·Insect Biochemistry and Molecular Biology·Z ChenP Batterham
Oct 5, 2002·Science·Hilary RansonRené Feyereisen
Jan 23, 2003·Bioinformatics·Charles S Bond
Mar 26, 2004·Insect Biochemistry and Molecular Biology·R HeidariR J Russell
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Mar 18, 2006·Molecular & Cellular Proteomics : MCP·Mathias BellerRonald P Kühnlein
Jun 10, 2006·The EMBO Journal·Jacques-Philippe ColletierMartin Weik
Aug 25, 2006·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Jul 30, 2008·Bioinformatics·Romain GautierGuillaume Drin
Oct 25, 2008·Nucleic Acids Research·Susan TweedieUNKNOWN FlyBase Consortium
Nov 4, 2008·Journal of the American Chemical Society·Eugénie CarlettiFlorian Nachon
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
May 26, 2009·Nucleic Acids Research·Thomas MargrafAndrew E Torda
Jun 11, 2009·Protein and Peptide Letters·Paul D Carr, David L Ollis
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
May 6, 2011·Nucleic Acids Research·Andrea PierleoniRita Casadio
Dec 27, 2011·Insect Biochemistry and Molecular Biology·Ruth Birner-GruenbergerRonald P Kühnlein
Apr 24, 2012·Chemistry & Biology·Moshe GoldsmithDan S Tawfik

❮ Previous
Next ❯

Citations

Mar 22, 2014·PLoS Neglected Tropical Diseases·Rodolphe PoupardinHilary Ranson
Mar 27, 2016·Journal of Molecular Biology·Nicholas J FraserColin J Jackson
May 8, 2015·Applied Microbiology and Biotechnology·Nina LülsdorfUlrich Schwaneberg
Nov 26, 2013·Aquatic Toxicology·Cathy A LaetzNathaniel L Scholz
Jun 6, 2015·Pesticide Biochemistry and Physiology·René FeyereisenThomas Van Leeuwen
Feb 7, 2017·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Alison Henrique Ferreira JulioAna Silvia Lapenta
Jul 13, 2017·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Luo-Luo WangJin-Jun Wang
Apr 29, 2014·Applied and Environmental Microbiology·Colin J JacksonColin Scott
Oct 13, 2018·Annual Review of Entomology·Sheng LiQili Feng
Dec 8, 2015·Nature Communications·Pierre-Yves ColinFlorian Hollfelder
Oct 3, 2019·Proceedings of the National Academy of Sciences of the United States of America·Galen J CorreyNir London
Oct 24, 2019·Biochemical Society Transactions·David CoombesRenwick C J Dobson
Nov 18, 2018·The Journal of Heredity·Rahul V RaneJohn G Oakeshott
Mar 30, 2018·Frontiers in Pharmacology·Sofya V LushchekinaPatrick Masson
Aug 14, 2019·Protein Engineering, Design & Selection : PEDS·Ana L Alfaro-ChávezDavid L Ollis
Nov 13, 2020·Frontiers in Physiology·Xuechun Feng, Nannan Liu
Jan 30, 2021·Biotechnology Letters·Fei YinJianqin Zhang
Mar 3, 2019·Ecotoxicology and Environmental Safety·B GagnaireL P Belzunces
Apr 20, 2021·Frontiers in Physiology·Ricardo GodoyAna Mutis

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.