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Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase
Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9435594/ https://www.ncbi.nlm.nih.gov/pubmed/36048150 http://dx.doi.org/10.1107/S2059798322007082 |
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author | Krawczyk, Lucas Semwal, Shubham Soubhye, Jalal Lemri Ouadriri, Salma Prévost, Martin Van Antwerpen, Pierre Roos, Goedele Bouckaert, Julie |
author_facet | Krawczyk, Lucas Semwal, Shubham Soubhye, Jalal Lemri Ouadriri, Salma Prévost, Martin Van Antwerpen, Pierre Roos, Goedele Bouckaert, Julie |
author_sort | Krawczyk, Lucas |
collection | PubMed |
description | Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation. Here, a newly obtained crystal structure of MPO containing four disulfide-linked dimers and showing an elaborate collection of glycans is reported. These are compared with the glycans identified in proteomics studies and from 18 human MPO structures available in the PDB. The crystal structure also contains bound paroxetine, a blocker of serotonin reuptake that has previously been identified as an irreversible inhibitor of MPO, in the presence of thiocyanate, a physiological substrate of MPO. |
format | Online Article Text |
id | pubmed-9435594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-94355942022-09-19 Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase Krawczyk, Lucas Semwal, Shubham Soubhye, Jalal Lemri Ouadriri, Salma Prévost, Martin Van Antwerpen, Pierre Roos, Goedele Bouckaert, Julie Acta Crystallogr D Struct Biol Feature Articles Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation. Here, a newly obtained crystal structure of MPO containing four disulfide-linked dimers and showing an elaborate collection of glycans is reported. These are compared with the glycans identified in proteomics studies and from 18 human MPO structures available in the PDB. The crystal structure also contains bound paroxetine, a blocker of serotonin reuptake that has previously been identified as an irreversible inhibitor of MPO, in the presence of thiocyanate, a physiological substrate of MPO. International Union of Crystallography 2022-08-09 /pmc/articles/PMC9435594/ /pubmed/36048150 http://dx.doi.org/10.1107/S2059798322007082 Text en © Lucas Krawczyk et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
spellingShingle | Feature Articles Krawczyk, Lucas Semwal, Shubham Soubhye, Jalal Lemri Ouadriri, Salma Prévost, Martin Van Antwerpen, Pierre Roos, Goedele Bouckaert, Julie Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
title | Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
title_full | Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
title_fullStr | Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
title_full_unstemmed | Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
title_short | Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
title_sort | native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase |
topic | Feature Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9435594/ https://www.ncbi.nlm.nih.gov/pubmed/36048150 http://dx.doi.org/10.1107/S2059798322007082 |
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