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Solubilization and Humanization of Paraoxonase-1
Joint Authors
Cerasoli, Douglas M.
Lenz, David E.
Harsch, Christina Keventzidis
Otto, Tamara C.
Hoffman, Kathryn
Magliery, Thomas J.
Matic, George T.
Norris, Joseph R.
Sarkar, Mohosin
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-07
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Paraoxonase-1 (PON1) is a serum protein, the activity of which is related to susceptibility to cardiovascular disease and intoxication by organophosphorus (OP) compounds.
It may also be involved in innate immunity, and it is a possible lead molecule in the development of a catalytic bioscavenger of OP pesticides and nerve agents.
Human PON1 expressed in E.
coli is mostly found in the insoluble fraction, which motivated the engineering of soluble variants, such as G2E6, with more than 50 mutations from huPON1.
We examined the effect on the solubility, activity, and stability of three sets of mutations designed to solubilize huPON1 with fewer overall changes: deletion of the N-terminal leader, polar mutations in the putative HDL binding site, and selection of the subset of residues that became more polar in going from huPON1 to G2E6.
All three sets of mutations increase the solubility of huPON1; the HDL-binding mutant has the largest effect on solubility, but it also decreases the activity and stability the most.
Based on the G2E6 polar mutations, we “humanized” an engineered variant of PON1 with high activity against cyclosarin (GF) and found that it was still very active against GF with much greater similarity to the human sequence.
American Psychological Association (APA)
Sarkar, Mohosin& Harsch, Christina Keventzidis& Matic, George T.& Hoffman, Kathryn& Norris, Joseph R.& Otto, Tamara C.…[et al.]. 2012. Solubilization and Humanization of Paraoxonase-1. Journal of Lipids،Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-485007
Modern Language Association (MLA)
Sarkar, Mohosin…[et al.]. Solubilization and Humanization of Paraoxonase-1. Journal of Lipids No. 2012 (2012), pp.1-13.
https://search.emarefa.net/detail/BIM-485007
American Medical Association (AMA)
Sarkar, Mohosin& Harsch, Christina Keventzidis& Matic, George T.& Hoffman, Kathryn& Norris, Joseph R.& Otto, Tamara C.…[et al.]. Solubilization and Humanization of Paraoxonase-1. Journal of Lipids. 2012. Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-485007
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-485007