Nitric oxide synthase domains

Ghosh, D. K., Salerno, J. C., Nitric oxide synthases domain structure and alignment in enzyme function and control. Front. Biosci. 8 (2003),... 

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

The Ca2+-calmodulin complex may also activate nitric oxide synthase (NOS), which binds to a PDZ domain of PSD-95. Activated NOS produces NO from arginine NO, in turn, activates guanylate cyclase, the enzyme that catalyzes the conversion of GTP to the intracellular messenger cGMP, which activates protein kinase G (PKG). 

Kiselyov K, Mignery GA, Zhu MX, Muallem S 1999 The N-terminal domain of the IP3 receptor gates store-operated hTrp3 channels. Mol Cell 4 423-429 Lee HC 2000 NAADP An emerging calcium signaling molecule. J Membr Biol 173 1 -8 Lin S, Fagan KA, Li K-X, Shaul PW, Cooper DMF, Rodman DM 2000 Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem 275 17979-17985... 

Siddhanta U., Presta, A., Fan, B., Wolan, D., Rousseau, D. L., Stuehr, D.)., Domain swapping in inducible nitric-oxide synthase. Electron transfer occurs between flavin and heme groups located on adjacent subunits in the dimmer, J. Biol. Chem. 273 (1998), p. 18950-18958... 

E. D., Stuehr, D. J.,Tainer, J. A., The structure of nitric oxide synthase oxygenase domain and inhibitor complexes, Science 278 (1997),... 

Li, H., Raman, C. S., Glaser, C. B., Blasko, E., Young,T. A., Parkinson, J. F., Whitlow, M., Poulos. T. L., Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase, ]. Biol.Chem. 

Upon binding calcium ions, the small acidic protein known as calmodulin can activate enzymes by binding to a wide variety of proteins containing cahnodulin-binding domains. Such proteins include cAMP phosphodiesterase, calmodulin-dependent nitric oxide synthase, calmodulin kinases, the plasma membrane calcium pump, calcineurin, and calmodulin-dependent inositol-(l,4,5)-trisphosphate 3-kinase. See also Activation Autoinhibition... 

AC VIII, adenylyl cyclase type VIII BDNF, brain-derived neurotrophic factor CamKII, calcium-calmodulin kinase II GIRK2, G protein-activated inward rectifying potassium 2 MAOA, monoamine oxidase A n.d., not determined NCAM, neural cell adhesion molecule nNOS, neuronal nitric oxide synthase Petl, ETS domain transcription factor tPA, serine protease tissue-plasminogen activator (tPA). t/ > Increase/decrease in anxiety-related behavior. No effect. 

Figure 3 Schematic representation of nitric oxide synthase isoforms and cytochrome P450 reductase. Haem, heme PDZ, PDZ domain (GLGF repeats) CaM, calmodulin FMN, flavin mononucleotide FAD, flavin adenine dinucleotide (adapted from Hobbs et al., 1999).

Ghosh S, Gachhui R, Crooks C, Wu C, Lisanti MP, Stuehr DJ. 1998. Interaction between caveolin-1 and the reductase domain of endothelial nitric-oxide synthase. Consequences for catalysis. J Biol Chem 273 22267-22271. 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, et al. (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains. Cell 84 757-67 Broillet MC, Firestein S (1996) Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron 16 377-85... 

Proteins associated with the PDZ ligand of the 5-HT4e receptor C-terminus are completely different from those that bind to the 5-HT4a receptors. They include the neuronal isoform of nitric oxide synthase (nNOS) and CIPP, two PDZ-domain-containing proteins, and Sec 23, which lacks any obvious PDZ domain (9). Sec 23 is a member of a protein complex designated as COPII, which is involved in the budding of vesicles from the endoplasmic reticulum (ER) and ER-to-Golgi transport of proteins. 

PTPS (6-Pyruvoyl Tetmhydropterin Synthase). 6-Pyruvoyl tetrahy-dropterin synthase catalyzes formation of tetrahydrobiopterin biosynthesis. Tetrahydrobiopterin is a cofactor for several important enzymes, such as aromatic amino acid hydroxylases and nitric oxide synthase (57). H. pylori protein HPAG1 0913 shares homology with members of the protein domain family PTPS. H. pylori protein shares poor sequence identity of 14% with the PTPS profile at an E-value of 10 10 and covers about 95% of the length of the profile. Fold recognition results also confirm the relationship between H. pylori protein and the PTPS protein domain family. A fold recognition algorithm ensures fitness of the H. pylori protein sequence on the three-dimensional structure of PTPS from... 

Feng C, Thomas C, Holliday MA, et al. Direct measurement by laser flash photolysis of intramolecular electron transfer in a two-domain construct of murine inducible nitric oxide synthase. J Am Chem Soc 2006 128 3808-11. 

Figure 2 Nitric oxide synthase, (a). Domain architecture of NOS. The heme domain binds Zn + (gray box), heme (gray parallelogram), and H4B (white box). The reductase domain binds FMN, FAD, and NADPH (white boxes). CaM (white box) is between the heme domain and the reductase domain, (b). Two-step reaction scheme for NO synthesis by NOS.

Hurshman AR, Krebs C, Edmondson DE, Huynh BH, Marietta MA. Formation of a pterin radical in the reaction of the heme domain of inducible nitric oxide synthase with oxygen. Biochemistry 1999 38 15689-15696. 

Venema, R., Sayegh, HS, Kent, JD, and Harrison, DG. 19%. Identification, characterization, and comparison of the calmodulin-binding domains of the endothelial and inducible nitric oxide synthases. J Biol Chem 271 6435-6440. 

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