Wu, Liang orcid.org/0000-0003-0294-7065, Jiang, Jianbing, Jin, Yi orcid.org/0000-0002-6927-4371 et al. (12 more authors) (2017) Activity-based probes for functional interrogation of retaining β-glucuronidases. NATURE CHEMICAL BIOLOGY. pp. 867-873. ISSN 1552-4450
Abstract
Humans express at least two distinct β-glucuronidase enzymes that are involved in disease: exo-acting β-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of β-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states. Unexpectedly, we find that the supposedly inactive HPSE proenzyme proHPSE is also labeled by our ABPs, leading to surprising insights regarding structural relationships between proHPSE, mature HPSE, and their bacterial homologs. Our results demonstrate the application of β-glucuronidase ABPs in tracking pathologically relevant enzymes and provide a case study of how ABP-driven approaches can lead to discovery of unanticipated structural and biochemical functionality.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number EUROPEAN COMMISSION 322942 |
Depositing User: | Pure (York) |
Date Deposited: | 06 Jun 2017 14:45 |
Last Modified: | 16 Oct 2024 13:38 |
Published Version: | https://doi.org/10.1038/nchembio.2395 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/nchembio.2395 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:117420 |