Details:

Alternative Title:
Biochemistry
Publisher's site:
http://dx.doi.org/10.1021/bi301024e
Personal Author:
Tyurin, Vladimir A. ; Yanamala, Naveena ; Tyurina, Yulia Y. ; Klein-Seetharaman, Judith ; Macphee, Colin H. ; ... More +
Tyurin, Vladimir A. ; Yanamala, Naveena ; Tyurina, Yulia Y. ; Klein-Seetharaman, Judith ; Macphee, Colin H. ; Kagan, Valerian E. Less -
Description:
Ca(2+)-independent lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a member of the phospholipase A(2) superfamily with a distinguishing characteristic of high specificity for oxidatively modified sn-2 fatty acid residues in phospholipids that has been especially well characterized for peroxidized species of phosphatidylcholines (PC). The ability of Lp-PLA(2) to hydrolyze peroxidized species of phosphatidylserine (PS), acting as a recognition signal for clearance of apoptotic cells by professional phagocytes, as well as the products of the reaction has not been investigated. We performed liquid chromatography-electrospray ionization mass spectrometry-based structural characterization of oxygenated, hydrolyzed molecular species of PS-containing linoleic acid in either the sn-2 position (C(18:0)/C(18:2)) or in both sn-1 and sn-2 positions (C(18:2)/C(18:2)), formed in the cytochrome c- and H(2)O(2)-driven enzymatic oxidation reaction. Cytochrome c has been chosen as a catalyst of peroxidation reactions because of its likely involvement in PS oxidation in apoptotic cells. We found that Lp-PLA(2) catalyzed the hydrolysis of both nontruncated and truncated (oxidatively fragmented) species of oxidized PS species, albeit with different efficiencies, and performed detailed characterization of the major reaction products: oxygenated derivatives of linoleic acid as well as nonoxygenated and oxygenated species of lyso-PS. Among linoleic acid products, derivatives oxygenated at the C(9) position, including 9-hydroxyoctadecadienoic acid (9-HODE), a potent ligand of G protein-coupled receptor G2A, were the most abundant. Computer modeling of interactions of Lp-PLA(2) with different PS-oxidized species indicated that they are able to bind in the proximity (<5 Å) of Ser273 and His351 of the catalytic triad. For 9-hydroxy and 9-hydroperoxy derivatives of oxidized PS, the sn-2 ester bond was positioned very close (<3 Å) to the Ser273 residue, a nucleophile directly attacking the sn-2 bond, thus favoring the hydrolysis reaction. We suggest that oxidatively modified free fatty acids and lyso-PS species generated by Lp-PLA(2) may represent important signals facilitating and regulating the execution of apoptotic and phagocytosis programs essential for the control of inflammation.
Subject:
[+]
1-Alkyl-2-acetylglycerophosphocholine Esterase
Article
Chromatography, Liquid
Computer Simulation
Molecular Docking Simulation
Phosphatidylserines
Spectrometry, Mass, Electrospray Ionization

Source:
Biochemistry. 51(48):9736-9750.
Pubmed ID:
23148485
Pubmed Central ID:
PMC3567262
Document Type:
Journal Article
Funding:
ES020693/ES/NIEHS NIH HHS/United States ; ES021068/ES/NIEHS NIH HHS/United States ; HL70755/HL/NHLBI NIH HHS/United States ; NS076511/NS/NINDS NIH HHS/United States ; OH008282/OH/NIOSH CDC HHS/United States ; ... More +
ES020693/ES/NIEHS NIH HHS/United States ; ES021068/ES/NIEHS NIH HHS/United States ; HL70755/HL/NHLBI NIH HHS/United States ; NS076511/NS/NINDS NIH HHS/United States ; OH008282/OH/NIOSH CDC HHS/United States ; R01 ES020693/ES/NIEHS NIH HHS/United States ; R01 HL070755/HL/NHLBI NIH HHS/United States ; R01 HL094488/HL/NHLBI NIH HHS/United States ; R01 NS076511/NS/NINDS NIH HHS/United States ; U19 AI068021/AI/NIAID NIH HHS/United States ; U19 AIO68021/PHS HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:c91c4e968be7728598c9aa0350e1760da0db4393a9bc9210e8cd29d356be2677
File Type:

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