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ABHD2 Inhibitor Identified by Activity-Based Protein Profiling Reduces Acrosome Reaction
[Image: see text] ABHD2 is a serine hydrolase that belongs to the subgroup of the α,β-hydrolase fold-containing proteins, which is involved in virus propagation, immune response, and fertilization. Chemical tools to selectively modulate the activity of ABHD2 in an acute setting are highly desired to...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878212/ https://www.ncbi.nlm.nih.gov/pubmed/31525885 http://dx.doi.org/10.1021/acschembio.9b00640 |
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author | Baggelaar, Marc P. den Dulk, Hans Florea, Bogdan I. Fazio, Domenico Bernabò, Nicola Raspa, Marcello Janssen, Antonius P. A. Scavizzi, Ferdinando Barboni, Barbara Overkleeft, Hermen S. Maccarrone, Mauro van der Stelt, Mario |
author_facet | Baggelaar, Marc P. den Dulk, Hans Florea, Bogdan I. Fazio, Domenico Bernabò, Nicola Raspa, Marcello Janssen, Antonius P. A. Scavizzi, Ferdinando Barboni, Barbara Overkleeft, Hermen S. Maccarrone, Mauro van der Stelt, Mario |
author_sort | Baggelaar, Marc P. |
collection | PubMed |
description | [Image: see text] ABHD2 is a serine hydrolase that belongs to the subgroup of the α,β-hydrolase fold-containing proteins, which is involved in virus propagation, immune response, and fertilization. Chemical tools to selectively modulate the activity of ABHD2 in an acute setting are highly desired to investigate its biological role, but are currently lacking. Here, we report a library-versus-library screening using activity-based protein profiling (ABPP) to evaluate in parallel the selectivity and activity of a focused lipase inhibitor library against ABHD2 and a panel of closely related ABHD proteins. This screen resulted in the rapid identification of novel inhibitors for ABHD2. The selectivity of the inhibitor was further investigated in native mouse testis proteome by competitive ABPP, revealing a highly restricted off-target profile. The progesterone-induced acrosome reaction was reduced in a dose-dependent manner by the newly identified inhibitor, which provides further support for the key-role of ABHD2 in the P4-stimulated acrosome reaction. On this basis, the ABHD2 inhibitor is an excellent starting point for further optimization of ABHD2 inhibitors that can modulate sperm fertility and may lead to novel contraceptives. |
format | Online Article Text |
id | pubmed-6878212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-68782122019-11-27 ABHD2 Inhibitor Identified by Activity-Based Protein Profiling Reduces Acrosome Reaction Baggelaar, Marc P. den Dulk, Hans Florea, Bogdan I. Fazio, Domenico Bernabò, Nicola Raspa, Marcello Janssen, Antonius P. A. Scavizzi, Ferdinando Barboni, Barbara Overkleeft, Hermen S. Maccarrone, Mauro van der Stelt, Mario ACS Chem Biol [Image: see text] ABHD2 is a serine hydrolase that belongs to the subgroup of the α,β-hydrolase fold-containing proteins, which is involved in virus propagation, immune response, and fertilization. Chemical tools to selectively modulate the activity of ABHD2 in an acute setting are highly desired to investigate its biological role, but are currently lacking. Here, we report a library-versus-library screening using activity-based protein profiling (ABPP) to evaluate in parallel the selectivity and activity of a focused lipase inhibitor library against ABHD2 and a panel of closely related ABHD proteins. This screen resulted in the rapid identification of novel inhibitors for ABHD2. The selectivity of the inhibitor was further investigated in native mouse testis proteome by competitive ABPP, revealing a highly restricted off-target profile. The progesterone-induced acrosome reaction was reduced in a dose-dependent manner by the newly identified inhibitor, which provides further support for the key-role of ABHD2 in the P4-stimulated acrosome reaction. On this basis, the ABHD2 inhibitor is an excellent starting point for further optimization of ABHD2 inhibitors that can modulate sperm fertility and may lead to novel contraceptives. American Chemical Society 2019-09-17 2019-10-18 /pmc/articles/PMC6878212/ /pubmed/31525885 http://dx.doi.org/10.1021/acschembio.9b00640 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Baggelaar, Marc P. den Dulk, Hans Florea, Bogdan I. Fazio, Domenico Bernabò, Nicola Raspa, Marcello Janssen, Antonius P. A. Scavizzi, Ferdinando Barboni, Barbara Overkleeft, Hermen S. Maccarrone, Mauro van der Stelt, Mario ABHD2 Inhibitor Identified by Activity-Based Protein Profiling Reduces Acrosome Reaction |
title | ABHD2 Inhibitor Identified by Activity-Based Protein
Profiling Reduces Acrosome Reaction |
title_full | ABHD2 Inhibitor Identified by Activity-Based Protein
Profiling Reduces Acrosome Reaction |
title_fullStr | ABHD2 Inhibitor Identified by Activity-Based Protein
Profiling Reduces Acrosome Reaction |
title_full_unstemmed | ABHD2 Inhibitor Identified by Activity-Based Protein
Profiling Reduces Acrosome Reaction |
title_short | ABHD2 Inhibitor Identified by Activity-Based Protein
Profiling Reduces Acrosome Reaction |
title_sort | abhd2 inhibitor identified by activity-based protein
profiling reduces acrosome reaction |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878212/ https://www.ncbi.nlm.nih.gov/pubmed/31525885 http://dx.doi.org/10.1021/acschembio.9b00640 |
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