Binding and activation of nitric oxide synthase isozymes by calmodulin EF hand pairs

The FEBS Journal
Donald E SprattJ G Guillemette

Abstract

Calmodulin (CaM) is a cytosolic Ca(2+) signal-transducing protein that binds and activates many different cellular enzymes with physiological relevance, including the nitric oxide synthase (NOS) isozymes. CaM consists of two globular domains joined by a central linker; each domain contains an EF hand pair. Four different mutant CaM proteins were used to investigate the role of the two CaM EF hand pairs in the binding and activation of the mammalian inducible NOS (iNOS) and the constitutive NOS (cNOS) enzymes, endothelial NOS (eNOS) and neuronal NOS (nNOS). The role of the CaM EF hand pairs in different aspects of NOS enzymatic function was monitored using three assays that monitor electron transfer within a NOS homodimer. Gel filtration studies were used to determine the effect of Ca(2+) on the dimerization of iNOS when coexpressed with CaM and the mutant CaM proteins. Gel mobility shift assays were performed to determine binding stoichiometries of CaM proteins to synthetic NOS CaM-binding domain peptides. Our results show that the N-terminal EF hand pair of CaM contains important binding and activating elements for iNOS, whereas the N-terminal EF hand pair in conjunction with the central linker region is required for cNOS enzy...Continue Reading

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Citations

Oct 3, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Changjian FengDipak K Ghosh
Aug 20, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·Changjian Feng, Gordon Tollin
Sep 10, 2009·The Journal of Biological Chemistry·Chuanwu XiaJung-Ja P Kim
Jun 10, 2010·The Journal of Biological Chemistry·Jesús TejeroDennis J Stuehr
Dec 29, 2010·Biochemistry Research International·Heather J MontgomeryJ Guy Guillemette
Oct 11, 2008·Biochimica Et Biophysica Acta·Donald E SprattJ Guy Guillemette
Sep 25, 2007·Biochimica Et Biophysica Acta·Donald E SprattJ Guy Guillemette
Jul 6, 2014·Fish & Shellfish Immunology·Shuo LiJinsheng Sun
Jan 26, 2017·Biochemistry·Michael PiazzaJ Guy Guillemette
May 24, 2013·International Journal of Molecular Sciences·Anna BogdanovaLars Kaestner
Jan 30, 2007·Journal of Medicinal Chemistry·Mark R BurnsSunil A David
Apr 12, 2007·Journal of the American Chemical Society·Changjian FengDipak K Ghosh
Jul 19, 2011·Journal of Inorganic Biochemistry·Gang WuAh-Lim Tsai

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