The structure and function of paraoxonase-1 and its comparison to paraoxonase-2 and -3

Taler-Verčič, Ajda (author), Goličnik, Marko (author), Bavec, Aljoša (author)

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.

• Language: English
• Keywords: paraoxonase, lactonase, oxidative stress, PON1, PON2, PON3, arylesterase, organophosphate, structure, kinetic, atherosclerosis
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 20 str.
• Numbering: Vol. 25, iss. 24, art. 5980
• PID: 20.500.12556/RUL-134835
• UDC: 577
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules25245980
• COBISS.SI-ID: 43242755
• Publication date in RUL: 03.02.2022

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 17.12.2020

Secondary language

• Language: Slovenian
• Keywords: paraoksonaza, laktonaza, oksidativni stres

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku