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Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure
In an effort to examine similarities in the active sites of glycosidases within the GH35 family, we performed a structure-activity-relationship study using our recently described library of galactonoamidines. The kinetic evaluation based on UV/Vis spectroscopy disclosed inhibition of β-galactosidase...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632213/ https://www.ncbi.nlm.nih.gov/pubmed/28844803 http://dx.doi.org/10.1016/j.bmc.2017.07.020 |
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author | Pickens, Jessica B. Wang, Feng Striegler, Susanne |
author_facet | Pickens, Jessica B. Wang, Feng Striegler, Susanne |
author_sort | Pickens, Jessica B. |
collection | PubMed |
description | In an effort to examine similarities in the active sites of glycosidases within the GH35 family, we performed a structure-activity-relationship study using our recently described library of galactonoamidines. The kinetic evaluation based on UV/Vis spectroscopy disclosed inhibition of β-galactosidase (bovine liver) in the picomolar concentration range indicating significantly higher inhibitor affinity than previously determined for β-galactosidase (A. oryzae). Possible alterations in the secondary protein structure or folding were excluded after further examination of the inhibitor binding using CD spectroscopy. Molecular dynamics studies suggested loop closing interactions as a rationale for the disparity of the active sites in the β-galactosidases under investigation. |
format | Online Article Text |
id | pubmed-5632213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-56322132018-10-15 Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure Pickens, Jessica B. Wang, Feng Striegler, Susanne Bioorg Med Chem Article In an effort to examine similarities in the active sites of glycosidases within the GH35 family, we performed a structure-activity-relationship study using our recently described library of galactonoamidines. The kinetic evaluation based on UV/Vis spectroscopy disclosed inhibition of β-galactosidase (bovine liver) in the picomolar concentration range indicating significantly higher inhibitor affinity than previously determined for β-galactosidase (A. oryzae). Possible alterations in the secondary protein structure or folding were excluded after further examination of the inhibitor binding using CD spectroscopy. Molecular dynamics studies suggested loop closing interactions as a rationale for the disparity of the active sites in the β-galactosidases under investigation. 2017-07-13 2017-10-15 /pmc/articles/PMC5632213/ /pubmed/28844803 http://dx.doi.org/10.1016/j.bmc.2017.07.020 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This manuscript version is made available under the CC BY-NC-ND 4.0 license. |
spellingShingle | Article Pickens, Jessica B. Wang, Feng Striegler, Susanne Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
title | Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
title_full | Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
title_fullStr | Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
title_full_unstemmed | Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
title_short | Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
title_sort | picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632213/ https://www.ncbi.nlm.nih.gov/pubmed/28844803 http://dx.doi.org/10.1016/j.bmc.2017.07.020 |
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