Functional and structural studies of a Phospholipase A2 -like protein complexed to zinc ions: Insights on its myotoxicity and inhibition mechanism

Biochimica Et Biophysica Acta. General Subjects
Rafael J BorgesM R M Fontes

Abstract

One of the main challenges in snakebite envenomation treatment is the development of stable, versatile and efficient anti-venom therapies. Local myotoxicity in accidents involving snakes from the Bothrops genus is still a consequence of serum therapy inefficient neutralization that may lead to permanent sequelae in their victims. One of the classes of toxins that participate in muscle necrosis is the PLA2-like proteins. The aim of this work was to investigate the role of zinc ions in the inhibition of PLA2-like proteins and to advance the current knowledge of their action mechanism. Myographic and electrophysiological techniques were used to evaluate the inhibitory effect of zinc ions, isothermal titration calorimetry assays were used to measure the affinity between zinc ions and the toxin and X-ray crystallography was used to reveal details of this interaction. We demonstrated that zinc ions can effectively inhibit the toxin by the interaction with two different sites, which are related to two different mechanism of inhibition: preventing membrane disruption and impairing the toxin state transition. Furthermore, structural study presented here included an additional step in the current myotoxic mechanism improving the comprehe...Continue Reading

References

Oct 1, 1992·Toxicon : Official Journal of the International Society on Toxinology·N F HeluanyL Rodrigues-Simioni
Jan 1, 1988·Toxicon : Official Journal of the International Society on Toxinology·M I Homsi-BrandeburgoJ R Giglio
Sep 1, 1974·Neuropharmacology·E K SilbergeldA M Goldberg
Nov 1, 1995·Toxicon : Official Journal of the International Society on Toxinology·L Rodrigues-SimioniJ E Fletcher
Mar 11, 1998·Biological Trace Element Research·A GölgeliS Aydogan
May 1, 1965·The Journal of General Physiology·F R CIOFALO, L J THOMAS
Sep 25, 2003·Toxicon : Official Journal of the International Society on Toxinology·Maristela de OliveiraMárcia Gallacci
Mar 17, 2004·Toxicon : Official Journal of the International Society on Toxinology·Andreimar M Soares, José R Giglio
Mar 17, 2004·Toxicon : Official Journal of the International Society on Toxinology·Bruno LomonteLeonel Calderón
Jul 1, 2004·Toxicon : Official Journal of the International Society on Toxinology·Vitelbina NúñezBruno Lomonte
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
May 1, 1995·Acta Crystallographica. Section D, Biological Crystallography·R K ArniA Tulinsky
Oct 27, 2004·Basic & Clinical Pharmacology & Toxicology·Yoko Oshima-FrancoLéa Rodrigues-Simioni
Dec 15, 2004·The Journal of Biological Chemistry·Andre L B AmbrosioRichard C Garratt
Jun 18, 2005·Journal of Molecular Biology·Mário T MurakamiRaghuvir K Arni
Jul 5, 2005·Toxicon : Official Journal of the International Society on Toxinology·Fábio K TicliSuely V Sampaio
Oct 27, 2005·Current Medicinal Chemistry·Andreimar M SoaresPaulo S Pereira
Sep 16, 2006·Biochimica Et Biophysica Acta·Ralph H Schaloske, Edward A Dennis
Dec 13, 2006·Toxicon : Official Journal of the International Society on Toxinology·Mário T MurakamiRaghuvir K Arni
Apr 25, 2007·Nucleic Acids Research·Ian W DavisDavid C Richardson
Jul 11, 2007·Journal of Mass Spectrometry : JMS·Juan J CalveteLibia Sanz
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Aug 8, 2008·Immunopharmacology and Immunotoxicology·Elda E Sánchez, Alexis Rodríguez-Acosta
May 20, 2009·Toxicon : Official Journal of the International Society on Toxinology·Arthur H C de OliveiraRichard J Ward
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 30, 2010·Lancet·David A Warrell
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Feb 16, 2010·Nutrition and Cancer·Ananda S PrasadOmer Kucuk
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jun 1, 2010·Experimental Biology and Medicine·Rebecca A BozymRichard B Thompson
Oct 19, 2010·Nutrition·Peter J LittleIrina L Korichneva
Jun 9, 2012·Toxicon : Official Journal of the International Society on Toxinology·Paola Rey-SuárezBruno Lomonte
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Aug 2, 2012·Nutrients·Bruce J Grattan, Hedley C Freake
Sep 22, 2012·Biochemical and Biophysical Research Communications·Pablo Javier Yunes QuartinoGerardo Daniel Fidelio
Apr 2, 2013·Toxicon : Official Journal of the International Society on Toxinology·Rafael Stuani FlorianoLéa Rodrigues-Simioni
Jul 3, 2013·Toxicon : Official Journal of the International Society on Toxinology·Guilherme H M SalvadorMarcos R M Fontes

❮ Previous
Next ❯

Citations

Jan 10, 2018·Toxins·Vanessa O ZambelliYara Cury
Nov 16, 2017·Scientific Reports·Rafael J BorgesMarcos R M Fontes
Nov 22, 2019·Scientific Reports·Guilherme H M SalvadorMarcos R M Fontes

❮ 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.

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.

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.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies 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.

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.

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.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.