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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/21/6736 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:55:06Z |
| format | Article |
| id | doaj.art-b64edf9ce0dd45f1a826e2f0774f55c1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:55:06Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b64edf9ce0dd45f1a826e2f0774f55c12023-11-22T21:25:51ZengMDPI AGMolecules1420-30492021-11-012621673610.3390/molecules26216736Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant <i>Staphylococcus aureus</i> through Computer-Assisted Drug DesignLluvia Rios-Soto0Alfredo Téllez-Valencia1Erick Sierra-Campos2Mónica Valdez-Solana3Jorge Cisneros-Martínez4Marcelo Gómez Palacio-Gastélum5Adriana Castillo-Villanueva6Claudia Avitia-Domínguez7Facultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Av. Universidad y Fanny Anitua S/N, Durango 34000, MexicoFacultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Av. Universidad y Fanny Anitua S/N, Durango 34000, MexicoFacultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 S/N Fracc. Filadelfia, Gómez Palacio, Durango 35010, MexicoFacultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 S/N Fracc. Filadelfia, Gómez Palacio, Durango 35010, MexicoFacultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Av. Universidad y Fanny Anitua S/N, Durango 34000, MexicoFacultad de Odontología, Universidad Juárez del Estado de Durango, Predio Canoas S/N, Los Angeles, Durango 34070, MexicoLaboratorio de Bioquímica-Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de Mexico 04530, MexicoFacultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Av. Universidad y Fanny Anitua S/N, Durango 34000, MexicoMethicillin-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.https://www.mdpi.com/1420-3049/26/21/6736MRSAshikimate kinasevirtual screeningmolecular dynamicsADME-Tox properties |
| spellingShingle | 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 Molecules MRSA shikimate kinase virtual screening molecular dynamics ADME-Tox properties |
| title | 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_short | 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 |
| topic | MRSA shikimate kinase virtual screening molecular dynamics ADME-Tox properties |
| url | https://www.mdpi.com/1420-3049/26/21/6736 |
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