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In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections

Naegleria fowleri, also known as the “brain-eating” amoeba, is a free-living protozoan that resides in freshwater bodies. This pathogenic amoeba infects humans as a casual event when swimming in contaminated water. Upon inhalation, N. fowleri invades the central nervous system and causes primary amo...

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Autores principales: Madero-Ayala, Pablo A., Mares-Alejandre, Rosa E., Ramos-Ibarra, Marco A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603766/
https://www.ncbi.nlm.nih.gov/pubmed/36293059
http://dx.doi.org/10.3390/ijms232012203
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author Madero-Ayala, Pablo A.
Mares-Alejandre, Rosa E.
Ramos-Ibarra, Marco A.
author_facet Madero-Ayala, Pablo A.
Mares-Alejandre, Rosa E.
Ramos-Ibarra, Marco A.
author_sort Madero-Ayala, Pablo A.
collection PubMed
description Naegleria fowleri, also known as the “brain-eating” amoeba, is a free-living protozoan that resides in freshwater bodies. This pathogenic amoeba infects humans as a casual event when swimming in contaminated water. Upon inhalation, N. fowleri invades the central nervous system and causes primary amoebic meningoencephalitis (PAM), a rapidly progressive and often fatal disease. Although PAM is considered rare, reducing its case fatality rate compels the search for pathogen-specific proteins with a structure–function relationship that favors their application as targets for discovering new or improved drugs against N. fowleri infections. Herein, we report a computational approach to study the structural features of Nf314 (a serine carboxypeptidase that is a virulence-related protein in N. fowleri infections) and assess its potential as a drug target, using bioinformatics tools and in silico molecular docking experiments. Our findings suggest that Nf314 has a ligand binding site suitable for the structure-based design of specific inhibitors. This study represents a further step toward postulating a reliable therapeutic target to treat PAM with drugs specifically aimed at blocking the pathogen proliferation by inhibiting protein function.
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spelling pubmed-96037662022-10-27 In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections Madero-Ayala, Pablo A. Mares-Alejandre, Rosa E. Ramos-Ibarra, Marco A. Int J Mol Sci Article Naegleria fowleri, also known as the “brain-eating” amoeba, is a free-living protozoan that resides in freshwater bodies. This pathogenic amoeba infects humans as a casual event when swimming in contaminated water. Upon inhalation, N. fowleri invades the central nervous system and causes primary amoebic meningoencephalitis (PAM), a rapidly progressive and often fatal disease. Although PAM is considered rare, reducing its case fatality rate compels the search for pathogen-specific proteins with a structure–function relationship that favors their application as targets for discovering new or improved drugs against N. fowleri infections. Herein, we report a computational approach to study the structural features of Nf314 (a serine carboxypeptidase that is a virulence-related protein in N. fowleri infections) and assess its potential as a drug target, using bioinformatics tools and in silico molecular docking experiments. Our findings suggest that Nf314 has a ligand binding site suitable for the structure-based design of specific inhibitors. This study represents a further step toward postulating a reliable therapeutic target to treat PAM with drugs specifically aimed at blocking the pathogen proliferation by inhibiting protein function. MDPI 2022-10-13 /pmc/articles/PMC9603766/ /pubmed/36293059 http://dx.doi.org/10.3390/ijms232012203 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Madero-Ayala, Pablo A.
Mares-Alejandre, Rosa E.
Ramos-Ibarra, Marco A.
In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections
title In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections
title_full In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections
title_fullStr In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections
title_full_unstemmed In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections
title_short In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections
title_sort in silico structural analysis of serine carboxypeptidase nf314, a potential drug target in naegleria fowleri infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603766/
https://www.ncbi.nlm.nih.gov/pubmed/36293059
http://dx.doi.org/10.3390/ijms232012203
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