Stability of highly purified human paraoxonase (PON1): association with human phosphate binding protein (HPBP) is essential for preserving its active conformation(s).


Abstract

The biological role of human paraoxonase (PON1) remains unclear, whilst there is a consensus that the enzyme has a protective influence. A toxicological role, protecting from environmental poisoning by organophosphate derivatives drove earlier works, and more recently, clinical interest has focused on a protective role in vascular disease. PON1 resides essentially on HDL particles, a complex and dynamic molecular environment. Our recent discovery of the human phosphate binding protein (HPBP), displaying a firm propensity to associate with PON1, has steered new directions for characterizing PON1 functional state. Here, we report investigations on the effect of HPBP on oligomerization, storage and thermal stability of PON1. We found that purified PON1 is as a mixture of at least two states, and that the absence of HPBP favors homo-oligomerization of PON1 into state(s) of higher molecular size. We showed that HPBP allows stabilizing active conformation(s) of PON1 disencumbered of its natural environment. We also showed that PON1 exhibits intrinsically a remarkable thermal stability, and that the association of HPBP strongly contributes to slow the denaturation rate. A hybrid recombinant PON1 was shown more thermostable than the human enzyme, and its stability was unaffected by the presence of HPBP. Altogether, the results strongly encourage further study of the human enzyme. Study holds ProTherm entries: 23060, 23061, 23062, 23063, 23064 Extra Details: Transition 2 (endothermic) Paraoxonase; Protein stability; Catalytic scavenger; Enzyme therapy; Nerve agent; Biopharmaceutical

Submission Details

ID: wXFabCu94

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:54 p.m.

Version: 1

Publication Details
Rochu D;Renault F;Cléry-Barraud C;Chabrière E;Masson P,Biochim. Biophys. Acta (2007) Stability of highly purified human paraoxonase (PON1): association with human phosphate binding protein (HPBP) is essential for preserving its active conformation(s). PMID:17556053
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1V04 2004-04-23 2.2 serum paraoxonase by directed evolution

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
90.7 Serum paraoxonase/arylesterase 1 P27170 PON1_RABIT
100.0 Serum paraoxonase/arylesterase 1 P27169 PON1_HUMAN