Role of the enzyme calmodulin-binding domain in membrane association and phospholipid inhibition of endothelial nitric oxide synthase.

The Journal of Biological Chemistry
R C VenemaD G Harrison

Abstract

Endothelial nitric oxide synthase (eNOS) is a calmodulin (CaM)-dependent, membrane-associated, myristoylated enzyme, which has an important role in regulation of vascular tone and platelet aggregation. In this study, wild-type and mutant forms of bovine eNOS were overexpressed in a baculovirus/Sf9 insect cell system and examined for interactions with membrane phospholipids. Purified wild-type eNOS binds to pure anionic phospholipid vesicles but not to neutral phospholipid vesicles, demonstrating that eNOS attachment to lipid bilayers requires electrostatic as well as hydrophobic interactions. Moreover, catalytic activity of the enzyme is potently inhibited by anionic phospholipids, notably phosphatidylserine (PS), but not by neutral phospholipids. eNOS activity is also significantly inhibited upon enzyme binding to biological membranes isolated from cultured cells. Binding of eNOS to PS vesicles prevents subsequent binding of the enzyme to CaM-Sepharose. Interactions of eNOS with PS are not affected by site-specific mutation of the myristic acid acceptor site in the enzyme. Deletional mutation of the eNOS CaM-binding domain, however, results in loss of binding capacity of the enzyme not only for CaM-Sepharose but also for PS ve...Continue Reading

References

May 1, 1992·Journal of Biochemistry·K HikiY Yui
Aug 1, 1992·The Journal of Experimental Medicine·H J ChoC Nathan
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D S Bredt, S H Snyder
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J S PollockF Murad
Feb 5, 1991·Biochemistry·P F Devaux
Feb 1, 1990·Trends in Biochemical Sciences·K T O'Neil, W F DeGrado
Nov 1, 1989·Archives of Biochemistry and Biophysics·A AsseffaF J Gonzalez
Jan 1, 1988·Annual Review of Biochemistry·D A TowlerL Glaser
Jan 1, 1980·Annual Review of Biophysics and Bioengineering·V Luzzati, A Tardieu
Jan 1, 1980·Annual Review of Biophysics and Bioengineering·F Szoka, D Papahadjopoulos
Apr 1, 1994·Journal of Neurochemistry·M HeckerR Busse
May 1, 1994·Journal of Vascular Research·W C Sessa
Sep 23, 1994·Cell·C Nathan, Q W Xie
Jan 20, 1995·The Journal of Biological Chemistry·L J RobinsonT Michel
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T MichelL Busconi
Apr 20, 1994·Biochimica Et Biophysica Acta·F Berthiaume, J A Frangos
Mar 1, 1994·The American Journal of Physiology·M J Kuchan, J A Frangos
Jan 1, 1993·Progress in Lipid Research·D Allan, K J Kallen

❮ Previous
Next ❯

Citations

Jun 8, 2001·Biochemical and Biophysical Research Communications·S J LeeJ T Stull
Sep 12, 2008·European Journal of Applied Physiology·M Brennan HarrisRichard C Venema
Sep 12, 2000·Current Hypertension Reports·R Busse, I Fleming
Dec 17, 1997·Clinical Biochemistry·L Mazzanti, B Mutus
Jan 13, 2000·Biophysical Chemistry·H Taniguchi
Jan 1, 1997·Trends in Cardiovascular Medicine·K Sase, T Michel
Apr 12, 2002·The International Journal of Biochemistry & Cell Biology·Elizabeth F da SilvaHelena M Scofano
Dec 20, 2002·International Immunopharmacology·Richard C Venema
Jun 1, 2006·Biochemistry·D J BlackAnthony Persechini
Oct 26, 2007·Biochemistry·D J BlackAnthony Persechini
Oct 8, 1999·The Biochemical Journal·M B MarreroR C Venema
Nov 9, 2000·The Plant Journal : for Cell and Molecular Biology·W A Snedden, E Blumwald
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·L J Robinson, T Michel
Apr 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H Kinoshita, Z S Katusic
Nov 7, 2001·Coronary Artery Disease·R K Kharbanda, J E Deanfield
Dec 31, 1997·The Journal of Clinical Investigation·D G Harrison
May 17, 2003·Drugs & Aging·Rachel L Matz, Ramaroson Andriantsitohaina
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·J IgarashiT Michel
Apr 13, 2013·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·David H JangRobert S Hoffman
Feb 5, 2011·The Journal of Nutritional Biochemistry·Joseph LayneBernhard Hennig
Aug 31, 2006·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·John N CurranDavid Bouchier-Hayes
Oct 21, 2006·Vascular Pharmacology·Gunay Yetik-Anacak, John D Catravas
Jul 27, 2007·Biochemical and Biophysical Research Communications·Masayuki SugimotoKozo Kaibuchi
Jun 1, 2001·Nitric Oxide : Biology and Chemistry·T Koeck, K Kremser
Mar 21, 1998·Cell Calcium·A ZahradníkováL G Mészáros
Sep 3, 1998·The Journal of Biological Chemistry·H JuR C Venema
Jun 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yiqun LingMichael B Fallon
Dec 17, 2008·Journal of Applied Physiology·Philip P Foster, Bruce D Butler
Feb 23, 2019·The Journal of Experimental Medicine·Lucía PiacenzaRafael Radi
May 11, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Helen M MarriottDavid H Dockrell

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.