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PON1 Structure

  • Denis Josse
  • Patrick Masson
  • Cynthia Bartels
  • Oksana Lockridge

Abstract

Paraoxonase (PON1) is an HDL-bound glycoprotein exhibiting calcium-dependent hydrolase and antioxidative activities, both related to distinct structural domains. Few structural data on PON1 and other related proteins, PON2 and 3, are currently available. The sequence of the 354 amino acid mature enzyme has been deduced from its cDNA. PON1 has 3 Cys residues: Cys-42 and -353 form a disulfide bond, Cys-284 is free. The PON1 hydrophobic N-terminus, predicted as an α-helix, is involved in the association of PON1 with phospholipids. The native enzyme purified from human plasma is not exclusively monomelic. The oligomeric state and size of human PON1 bound to non-ionic detergent molecules depends on the concentration of detergent. Five His (H115, H134, H155, H243, H285), 1 Trp (W281), 2 G1u (E53, E195) and 6 Asp (D54, D169, D183, D269, D279) residues are essential for human PON1 arylesterase and organophosphatase activities. The residues in position 192 and 284, although not essential for the PON1 hydrolase activity, could be close to the active site. PON1 shares common structural and functional features with other lactonohydrolases, mainly PON3. The PON1 3D structure will be established in the near future. It will help to relate PON1 structural and functional properties.

Key Words

paraoxonase organophosphate lactonohydrolase calcium-binding site-directed mutagenesis 

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Denis Josse
    • 1
  • Patrick Masson
    • 1
  • Cynthia Bartels
    • 2
  • Oksana Lockridge
    • 2
  1. 1.Unité d’enzymologieCentre de Recherches du Service de Santé des ArméesLa Tronche CedexFrance
  2. 2.Eppley InstituteUniversity of Nebraska Medical CenterOmahaUSA

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