Journal article

The mutation G133D on Leishmania guyanensis AQP1 is highly destabilizing as revealed by molecular modeling and hypo-osmotic shock assay

Luiza G Tunes, David B Ascher, Douglas E Pires, Rubens L Monte-Neto

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | ELSEVIER | Published : 2021

Abstract

The Leishmania aquaglyceroporin 1 (AQP1) plays an important role in osmoregulation and antimony (Sb) uptake, being determinant for resistance to antimony. We have previously demonstrated that G133D mutation on L. guyanensis AQP1 (LgAQP1) leads to reduced Sb uptake. Here, we investigated the effects of G133D mutation on LgAQP1 structure, associated with Sb uptake and alterations in osmoregulation capacity. High confidence molecular models of wild-type LgAQP1 as well as the LgAQP1::G133D mutant were constructed and optimized via comparative homology modeling. Computational methods from the mCSM platform were used to evaluate the effects on protein stability and on its ability to bind to glycer..

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Grants

Awarded by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq -Brasil)


Awarded by Jack Brockhoff Foundation


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by CNPq


Funding Acknowledgements

D.B.A and D.P. were funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq -Brasil) [409780/2016-2]; the Jack Brockhoff Foundation [JBF 4186, 2016]; and an Investigator Grant from the National Health and Medical Research Council (NHMRC) of Australia [GNT1174405]. Supported in part by the Victorian Government's OIS Program. R.M.N. is a CNPq research fellow (310640/2017-2) and was supported by CNPq grant number 429625/2016-2.