Stabilization of the active form(s) of human paraoxonase by human phosphate-binding protein

O. Rochu, E. Chabrière, F. Renault, M. Elias, C. Cléry-Barraud, P. Masson

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

While there is a consensus that human PON1 (paraoxonase-1) has a protective role, its primary biological function remains unclear. A protective role against poisoning by organophosphates [OPs (organophosphorus compounds)] drove earlier works. Clinical interest has recently focused on a protective role of PON1 against vascular diseases. PON1 resides mainly on HDL (high-density lipoprotein) particles, and converging recent works show that both its activities and stability dramatically depend on this versatile and dynamic molecular environment. The discovery that HPBP (human phosphate-binding protein) has a firm tendency to associate with PON1 has steered new directions for characterizing PON1 functional state(s). Storage stability studies provided evidence that HPBP is involved in maintaining physiologically active POM conformation(s). Thermal stability studies showed that human PON1 is remarkably thermostable and that its association with HPBP strongly contributes to slowing down the denaturation rate. A hybrid PON1, displaying mutations that stabilized recombinant enzyme expressed in Escherichia coli, was shown to be more thermostable than natural human PON1. Predictably, its stability was unaffected by the presence of HPBP. Synergistic efforts on characterizing natural PON1 and rPON1 (recombinant PON1) provide information for the design of future stable mutants of PON1 -based bioscavengers to be used as safe and effective countermeasures to challenge OPs. Maintaining a stable environment for such administrable human rPON1 should, at least, preserve the anti-atherogenic activity of the enzyme.

Original languageEnglish (US)
Pages (from-to)1616-1620
Number of pages5
JournalBiochemical Society transactions
Volume35
Issue number6
DOIs
StatePublished - Dec 1 2007

Keywords

  • Catalytic scavenger
  • Functional state
  • Human phosphate-binding protein
  • Paraoxonase
  • Protein stability
  • Purification

Fingerprint Dive into the research topics of 'Stabilization of the active form(s) of human paraoxonase by human phosphate-binding protein'. Together they form a unique fingerprint.

  • Cite this