دورية أكاديمية
أعرض في EDS

Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center.

التفاصيل البيبلوغرافية
العنوان: Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center.
المؤلفون: Cozza G; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Rossetto M; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Bosello-Travain V; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Maiorino M; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Roveri A; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Toppo S; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Zaccarin M; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Zennaro L; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy., Ursini F; Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy. Electronic address: fulvio.ursini@unipd.it.
المصدر: Free radical biology & medicine [Free Radic Biol Med] 2017 Nov; Vol. 112, pp. 1-11. Date of Electronic Publication: 2017 Jul 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE
أسماء مطبوعة: Publication: Tarrytown, NY : Elsevier Science
Original Publication: New York : Pergamon, c1987-
مواضيع طبية MeSH: Cardiolipins/*chemistry , Glutathione Peroxidase/*chemistry , Lipid Peroxides/*chemistry , Liposomes/*chemistry , Phosphatidylcholines/*chemistry, Amino Acid Sequence ; Animals ; Binding Sites ; Biocatalysis ; Cardiolipins/metabolism ; Gene Expression ; Glutathione Peroxidase/isolation & purification ; Glutathione Peroxidase/metabolism ; HEK293 Cells ; Humans ; Kinetics ; Lipid Peroxides/metabolism ; Liposomes/metabolism ; Male ; Molecular Docking Simulation ; Oxidation-Reduction ; Phosphatidylcholines/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Rats ; Sequence Alignment ; Sequence Homology, Amino Acid ; Static Electricity ; Substrate Specificity ; Testis/chemistry ; Testis/enzymology
مستخلص: GPx4 is a monomeric glutathione peroxidase, unique in reducing the hydroperoxide group (-OOH) of fatty acids esterified in membrane phospholipids. This reaction inhibits lipid peroxidation and accounts for enzyme's vital role. Here we investigated the interaction of GPx4 with membrane phospholipids. A cationic surface near the GPx4 catalytic center interacts with phospholipid polar heads. Accordingly, SPR analysis indicates cardiolipin as the phospholipid with maximal affinity to GPx4. Consistent with the electrostatic nature of the interaction, KCl increases the K D . Molecular dynamic (MD) simulation shows that a -OOH posed in the core of the membrane as 13 - or 9 -OOH of tetra-linoleoyl cardiolipin or 15 -OOH stearoyl-arachidonoyl-phosphaphatidylcholine moves to the lipid-water interface. Thereby, the -OOH groups are addressed toward the GPx4 redox center. In this pose, however, the catalytic site facing the membrane would be inaccessible to GSH, but the consecutive redox processes facilitate access of GSH, which further primes undocking of the enzyme, because GSH competes for the binding residues implicated in docking. During the final phase of the catalytic cycle, while GSSG is produced, GPx4 is disconnected from the membrane. The observation that GSH depletion in cells induces GPx4 translocation to the membrane, is in agreement with this concept.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: GPx4; Lipid peroxidation; Membrane; Molecular dynamics; PHGPx; SPR analysis; Selenocysteine
المشرفين على المادة: 0 (1,1',2,2'-tetraoleoylcardiolipin)
0 (Cardiolipins)
0 (Lipid Peroxides)
0 (Liposomes)
0 (Phosphatidylcholines)
EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
EC 1.11.1.9 (Glutathione Peroxidase)
EC 1.11.1.9 (glutathione peroxidase 4, rat)
EDS2L3ODLV (1,2-oleoylphosphatidylcholine)
تواريخ الأحداث: Date Created: 20170716 Date Completed: 20180523 Latest Revision: 20191210
رمز التحديث: 20240829
DOI: 10.1016/j.freeradbiomed.2017.07.010
PMID: 28709976
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4596
DOI:10.1016/j.freeradbiomed.2017.07.010