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The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3
Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascul...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766523/ https://www.ncbi.nlm.nih.gov/pubmed/33348669 http://dx.doi.org/10.3390/molecules25245980 |
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author | Taler-Verčič, Ajda Goličnik, Marko Bavec, Aljoša |
author_facet | Taler-Verčič, Ajda Goličnik, Marko Bavec, Aljoša |
author_sort | Taler-Verčič, Ajda |
collection | PubMed |
description | Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases. Although all three members of the PON family have the same origin and very similar amino acid sequences, they have different functions and are found in different locations. PONs exhibit substrate promiscuity, and their true physiological substrates are still not known. However, possible substrates include homocysteine thiolactone, an analogue of natural quorum-sensing molecules, and the recently discovered derivatives of arachidonic acid—bioactive δ-lactones. Directed evolution, site-directed mutagenesis, and kinetic studies provide comprehensive insights into the active site and catalytic mechanism of PON1. However, there is still a whole world of mystery waiting to be discovered, which would elucidate the substrate promiscuity of a group of enzymes that are so similar in their evolution and sequence yet so distinct in their function. |
format | Online Article Text |
id | pubmed-7766523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77665232020-12-28 The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 Taler-Verčič, Ajda Goličnik, Marko Bavec, Aljoša Molecules Review Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases. Although all three members of the PON family have the same origin and very similar amino acid sequences, they have different functions and are found in different locations. PONs exhibit substrate promiscuity, and their true physiological substrates are still not known. However, possible substrates include homocysteine thiolactone, an analogue of natural quorum-sensing molecules, and the recently discovered derivatives of arachidonic acid—bioactive δ-lactones. Directed evolution, site-directed mutagenesis, and kinetic studies provide comprehensive insights into the active site and catalytic mechanism of PON1. However, there is still a whole world of mystery waiting to be discovered, which would elucidate the substrate promiscuity of a group of enzymes that are so similar in their evolution and sequence yet so distinct in their function. MDPI 2020-12-17 /pmc/articles/PMC7766523/ /pubmed/33348669 http://dx.doi.org/10.3390/molecules25245980 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Taler-Verčič, Ajda Goličnik, Marko Bavec, Aljoša The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 |
title | The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 |
title_full | The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 |
title_fullStr | The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 |
title_full_unstemmed | The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 |
title_short | The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3 |
title_sort | structure and function of paraoxonase-1 and its comparison to paraoxonase-2 and -3 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766523/ https://www.ncbi.nlm.nih.gov/pubmed/33348669 http://dx.doi.org/10.3390/molecules25245980 |
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