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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...

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Autores principales: Taler-Verčič, Ajda, Goličnik, Marko, Bavec, Aljoša
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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