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Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus
Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116672/ https://www.ncbi.nlm.nih.gov/pubmed/30141354 http://dx.doi.org/10.1080/14756366.2018.1493474 |
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author | Borišek, Jure Pintar, Sara Ogrizek, Mitja Grdadolnik, Simona Golič Hodnik, Vesna Turk, Dušan Perdih, Andrej Novič, Marjana |
author_facet | Borišek, Jure Pintar, Sara Ogrizek, Mitja Grdadolnik, Simona Golič Hodnik, Vesna Turk, Dušan Perdih, Andrej Novič, Marjana |
author_sort | Borišek, Jure |
collection | PubMed |
description | Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target. |
format | Online Article Text |
id | pubmed-6116672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-61166722018-09-04 Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus Borišek, Jure Pintar, Sara Ogrizek, Mitja Grdadolnik, Simona Golič Hodnik, Vesna Turk, Dušan Perdih, Andrej Novič, Marjana J Enzyme Inhib Med Chem Research Paper Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target. Taylor & Francis 2018-08-24 /pmc/articles/PMC6116672/ /pubmed/30141354 http://dx.doi.org/10.1080/14756366.2018.1493474 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Borišek, Jure Pintar, Sara Ogrizek, Mitja Grdadolnik, Simona Golič Hodnik, Vesna Turk, Dušan Perdih, Andrej Novič, Marjana Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
title | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
title_full | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
title_fullStr | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
title_full_unstemmed | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
title_short | Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus |
title_sort | discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin e from staphylococcus aureus |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116672/ https://www.ncbi.nlm.nih.gov/pubmed/30141354 http://dx.doi.org/10.1080/14756366.2018.1493474 |
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