Characterization of the PON1 active site using modeling simulation, in relation to PON1 lactonase activity

Hagai Tavori, Soliman Khatib, Michael Aviram, Jacob Vaya

    Research output: Contribution to journalArticle

    33 Scopus citations

    Abstract

    Paraoxonase1 (PON1) is a HDL bound enzyme and many of the anti-atherogenic properties of HDL are attributed to PON1. The enzyme precise mechanism of protective action and its endogenous substrate remain elusive. PON1 hydrolyzes organophosphates, arylesters and lactones, whereas the lactones activity is assumed as the physio/pathological one. This study is aimed to predict the location of the PON1 active site within PON1 crystal structure, and the lactone structure suitability as PON1 ligand, by employing modeling techniques. Based on such calculations the ligands-PON1 interactions were characterized, and relating lactones rate of hydrolysis revealed an inverse correlation with the docking energy of the ligands-PON1 complex, and a direct correlation with the lactone side chain length. In conclusion, this study characterized the PON1 possible active site and proposes a tool which may make it possible to envisage the structure of potential endogenous and exogenous lactones such as the PON1 ligand.

    Original languageEnglish (US)
    Pages (from-to)7504-7509
    Number of pages6
    JournalBioorganic and Medicinal Chemistry
    Volume16
    Issue number15
    DOIs
    StatePublished - Aug 1 2008

    Keywords

    • Docking
    • Lactones
    • Lactonization
    • Modeling
    • Paraoxonase1

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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