Investigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibition

Handle URI:
http://hdl.handle.net/10754/598665
Title:
Investigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibition
Authors:
Caroli, Antonia; Simeoni, Silvia; Lepore, Rosalba; Tramontano, Anna; Via, Allegra
Abstract:
Schistosoma mansoni and Plasmodium falciparum are pathogen parasites that spend part of their lives in the blood stream of the human host and are therefore heavily exposed to fluxes of toxic reactive oxygen species (ROS). SmTGR, an essential enzyme of the S. mansoni ROS detoxification machinery, is known to be inhibited by Auranofin although the inhibition mechanism has not been completely clarified. Auranofin also kills P. falciparum, even if its molecular targets are unknown. Here, we used computational and docking techniques to investigate the molecular mechanism of interaction between SmTGR and Auranofin. Furthermore, we took advantage of the homology relationship and of docking studies to assess if PfTR, the SmTGR malaria parasite homologue, can be a putative target for Auranofin. Our findings support a recently hypothesized molecular mechanism of inhibition for SmTGR and suggest that PfTR is indeed a possible and attractive drug target in P. falciparum. © 2011 Elsevier Inc.
Citation:
Caroli A, Simeoni S, Lepore R, Tramontano A, Via A (2012) Investigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibition. Biochemical and Biophysical Research Communications 417: 576–581. Available: http://dx.doi.org/10.1016/j.bbrc.2011.12.009.
Publisher:
Elsevier BV
Journal:
Biochemical and Biophysical Research Communications
KAUST Grant Number:
KUK-I1-012-43
Issue Date:
Jan-2012
DOI:
10.1016/j.bbrc.2011.12.009
PubMed ID:
22177949
Type:
Article
ISSN:
0006-291X
Sponsors:
We thank the members of the Fondazione Roma Research Unit led by Prof. Maurizio Brunori for useful discussions and Prof. Arthur Lesk for critically reading the manuscript. This work was partially supported by Award number KUK-I1-012-43 made by King Abdullah University of Science and Technology (KAUST), FIRB Proteomica, Ministery of Health Grant Contract No. Onc_Ord 25/07, Fondazione Roma and the IIT SEED project.
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Full metadata record

DC FieldValue Language
dc.contributor.authorCaroli, Antoniaen
dc.contributor.authorSimeoni, Silviaen
dc.contributor.authorLepore, Rosalbaen
dc.contributor.authorTramontano, Annaen
dc.contributor.authorVia, Allegraen
dc.date.accessioned2016-02-25T13:34:04Zen
dc.date.available2016-02-25T13:34:04Zen
dc.date.issued2012-01en
dc.identifier.citationCaroli A, Simeoni S, Lepore R, Tramontano A, Via A (2012) Investigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibition. Biochemical and Biophysical Research Communications 417: 576–581. Available: http://dx.doi.org/10.1016/j.bbrc.2011.12.009.en
dc.identifier.issn0006-291Xen
dc.identifier.pmid22177949en
dc.identifier.doi10.1016/j.bbrc.2011.12.009en
dc.identifier.urihttp://hdl.handle.net/10754/598665en
dc.description.abstractSchistosoma mansoni and Plasmodium falciparum are pathogen parasites that spend part of their lives in the blood stream of the human host and are therefore heavily exposed to fluxes of toxic reactive oxygen species (ROS). SmTGR, an essential enzyme of the S. mansoni ROS detoxification machinery, is known to be inhibited by Auranofin although the inhibition mechanism has not been completely clarified. Auranofin also kills P. falciparum, even if its molecular targets are unknown. Here, we used computational and docking techniques to investigate the molecular mechanism of interaction between SmTGR and Auranofin. Furthermore, we took advantage of the homology relationship and of docking studies to assess if PfTR, the SmTGR malaria parasite homologue, can be a putative target for Auranofin. Our findings support a recently hypothesized molecular mechanism of inhibition for SmTGR and suggest that PfTR is indeed a possible and attractive drug target in P. falciparum. © 2011 Elsevier Inc.en
dc.description.sponsorshipWe thank the members of the Fondazione Roma Research Unit led by Prof. Maurizio Brunori for useful discussions and Prof. Arthur Lesk for critically reading the manuscript. This work was partially supported by Award number KUK-I1-012-43 made by King Abdullah University of Science and Technology (KAUST), FIRB Proteomica, Ministery of Health Grant Contract No. Onc_Ord 25/07, Fondazione Roma and the IIT SEED project.en
dc.publisherElsevier BVen
dc.subjectAuranofinen
dc.subjectP. falciparumen
dc.subjectS. mansonien
dc.subjectThioredoxin Glutathione Reductaseen
dc.titleInvestigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibitionen
dc.typeArticleen
dc.identifier.journalBiochemical and Biophysical Research Communicationsen
dc.contributor.institutionUniversita degli Studi di Roma La Sapienza, Rome, Italyen
kaust.grant.numberKUK-I1-012-43en

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