A Common Mutation in Paraoxonase-2 Results in Impaired Lactonase Activity

David A Stoltz; Egon A Ozer; Thomas J Recker; Miriam Estin; Xia Yang; Diana M Shih; Aldons J Lusis; Joseph Zabner

doi:10.1074/jbc.M109.051706

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A Common Mutation in Paraoxonase-2 Results in Impaired Lactonase Activity

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A Common Mutation in Paraoxonase-2 Results in Impaired Lactonase Activity

David A Stoltz, Egon A Ozer, Thomas J Recker, Miriam Estin, Xia Yang, Diana M Shih, Aldons J Lusis and Joseph Zabner

The Journal of biological chemistry, Vol.284(51), pp.35564-35571

12/18/2009

DOI: 10.1074/jbc.M109.051706

PMCID: PMC2790986

PMID: 19840942

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Abstract

Paraoxonases (PONs) are a family of lactonases with promiscuous enzyme activity that has been implicated in multiple diseases. PON2 is intracellularly located, is the most ubiquitously expressed PON, and has the highest lactonase activity of the PON family members. Whereas some single-nucleotide polymorphisms (SNPs) in PON1 have resulted in altered enzymatic activity in serum, to date the functional consequences of SNPs on PON2 function remain unknown. We hypothesized that a common PON2 SNP would result in impaired lactonase activity. Substitution of cysteine for serine at codon 311 in recombinant PON2 resulted in normal protein production and localization but altered glycosylation and decreased lactonase activity. Moreover, we screened 200 human lung samples for the PON2 Cys 311 variant and found that in vivo this mutation impaired lactonase activity. These data suggest that impaired lactonase activity may play a role in innate immunity, atherosclerosis, and other diseases associated with the PON2 311 SNP.

Genomics, Proteomics, and Bioinformatics

Details

Title: Subtitle: A Common Mutation in Paraoxonase-2 Results in Impaired Lactonase Activity
Creators: David A Stoltz - From the
Egon A Ozer - the
Thomas J Recker - From the
Miriam Estin - From the
Xia Yang - Rosetta Inpharmatics, Inc., Seattle, Washington 98109
Diana M Shih - the
Aldons J Lusis - the
Joseph Zabner - From the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.284(51), pp.35564-35571
DOI: 10.1074/jbc.M109.051706
PMID: 19840942
PMCID: PMC2790986
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: DK54759; AI076671; HL61234-09 / National Institutes of Health
Language: English
Date published: 12/18/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984025451502771

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