Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is an important threat as it causes serious hospital and community acquired infections with deathly outcomes oftentimes, therefore, development of new treatments against this bacterium is a priority. Shikimate kinase, an enzyme in...

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Autores principales: Lluvia Rios-Soto, Alfredo Téllez-Valencia, Erick Sierra-Campos, Mónica Valdez-Solana, Jorge Cisneros-Martínez, Marcelo Gómez Palacio-Gastélum, Adriana Castillo-Villanueva, Claudia Avitia-Domínguez
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:b64edf9ce0dd45f1a826e2f0774f55c12021-11-11T18:40:23ZFinding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design10.3390/molecules262167361420-3049https://doaj.org/article/b64edf9ce0dd45f1a826e2f0774f55c12021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6736https://doaj.org/toc/1420-3049Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is an important threat as it causes serious hospital and community acquired infections with deathly outcomes oftentimes, therefore, development of new treatments against this bacterium is a priority. Shikimate kinase, an enzyme in the shikimate pathway, is considered a good target for developing antimicrobial drugs; this is given because of its pathway, which is essential in bacteria whereas it is absent in mammals. In this work, a computer-assisted drug design strategy was used to report the first potentials inhibitors for Shikimate kinase from methicillin-resistant <i>Staphylococcus aureus</i> (SaSK), employing approximately 5 million compounds from ZINC15 database. Diverse filtering criteria, related to druglike characteristics and virtual docking screening in the shikimate binding site, were performed to select structurally diverse potential inhibitors from SaSK. Molecular dynamics simulations were performed to elucidate the dynamic behavior of each SaSK–ligand complex. The potential inhibitors formed important interactions with residues that are crucial for enzyme catalysis, such as Asp37, Arg61, Gly82, and Arg138. Therefore, the compounds reported provide valuable information and can be seen as the first step toward developing SaSK inhibitors in the search of new drugs against MRSA.Lluvia Rios-SotoAlfredo Téllez-ValenciaErick Sierra-CamposMónica Valdez-SolanaJorge Cisneros-MartínezMarcelo Gómez Palacio-GastélumAdriana Castillo-VillanuevaClaudia Avitia-DomínguezMDPI AGarticleMRSAshikimate kinasevirtual screeningmolecular dynamicsADME-Tox propertiesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6736, p 6736 (2021)
institution DOAJ
collection DOAJ
language EN
topic MRSA
shikimate kinase
virtual screening
molecular dynamics
ADME-Tox properties
Organic chemistry
QD241-441
spellingShingle MRSA
shikimate kinase
virtual screening
molecular dynamics
ADME-Tox properties
Organic chemistry
QD241-441
Lluvia Rios-Soto
Alfredo Téllez-Valencia
Erick Sierra-Campos
Mónica Valdez-Solana
Jorge Cisneros-Martínez
Marcelo Gómez Palacio-Gastélum
Adriana Castillo-Villanueva
Claudia Avitia-Domínguez
Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design
description Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is an important threat as it causes serious hospital and community acquired infections with deathly outcomes oftentimes, therefore, development of new treatments against this bacterium is a priority. Shikimate kinase, an enzyme in the shikimate pathway, is considered a good target for developing antimicrobial drugs; this is given because of its pathway, which is essential in bacteria whereas it is absent in mammals. In this work, a computer-assisted drug design strategy was used to report the first potentials inhibitors for Shikimate kinase from methicillin-resistant <i>Staphylococcus aureus</i> (SaSK), employing approximately 5 million compounds from ZINC15 database. Diverse filtering criteria, related to druglike characteristics and virtual docking screening in the shikimate binding site, were performed to select structurally diverse potential inhibitors from SaSK. Molecular dynamics simulations were performed to elucidate the dynamic behavior of each SaSK–ligand complex. The potential inhibitors formed important interactions with residues that are crucial for enzyme catalysis, such as Asp37, Arg61, Gly82, and Arg138. Therefore, the compounds reported provide valuable information and can be seen as the first step toward developing SaSK inhibitors in the search of new drugs against MRSA.
format article
author Lluvia Rios-Soto
Alfredo Téllez-Valencia
Erick Sierra-Campos
Mónica Valdez-Solana
Jorge Cisneros-Martínez
Marcelo Gómez Palacio-Gastélum
Adriana Castillo-Villanueva
Claudia Avitia-Domínguez
author_facet Lluvia Rios-Soto
Alfredo Téllez-Valencia
Erick Sierra-Campos
Mónica Valdez-Solana
Jorge Cisneros-Martínez
Marcelo Gómez Palacio-Gastélum
Adriana Castillo-Villanueva
Claudia Avitia-Domínguez
author_sort Lluvia Rios-Soto
title Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design
title_short Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design
title_full Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design
title_fullStr Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design
title_full_unstemmed Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug Design
title_sort finding the first potential inhibitors of shikimate kinase from methicillin resistant <i>staphylococcus aureus</i> through computer-assisted drug design
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/b64edf9ce0dd45f1a826e2f0774f55c1
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