A comparative study of the COX-1 and COX-2 isozymes bound to lipid membranes
2008 Wiley Periodicals, Inc.
| Publié dans: | Journal of computational chemistry. - 1984. - 30(2009), 7 vom: 01. Mai, Seite 1038-50 |
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| Auteur principal: | |
| Autres auteurs: | |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2009
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| Accès à la collection: | Journal of computational chemistry |
| Sujets: | Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Lipid Bilayers Membrane Lipids Water 059QF0KO0R Cyclooxygenase 1 EC 1.14.99.1 |
| Résumé: | 2008 Wiley Periodicals, Inc. The monotopic proteins COX-1 and -2 in dimeric form bound to lipid bilayer membranes are studied using molecular dynamics simulations within an aqueous environment. The 25-ns simulations are performed for both isozymes with arachidonic acid bound in the cyclooxygenase sites. The interactions between the enzymes and the lipids are analyzed, providing insight into the attachment mechanism of monotopic proteins to membranes. Our study reveals some key differences between the two isozymes that include the orientations at which they sit on the surface of the membranes and the depths to which they embed within the membranes. The differences in membrane association of the isozymes indicate that they may integrate distinctively with the same membrane, and/or with different membranes or their lipid components. Our results indicate that arachidonic acid can be bound in the cyclooxygenase active site in distinct catalytically competent conformations that lead to certain hydroperoxy acids; and the arachidonic acid and/or cyclooxygenase sites undergo a conformational change which makes only one subunit of each homodimer catalytically active |
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| Description: | Date Completed 24.06.2009 Date Revised 29.05.2025 published: Print Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.21130 |