- NOS1
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Nitric oxide synthase 1 (neuronal), also known as NOS1, is an enzyme that in humans is encoded by the NOS1 gene.[1][2]
Contents
Function
Nitric oxide (NO) is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter; it is implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. NO is also responsible for endothelium-derived relaxing factor activity regulating blood pressure. In macrophages, NO mediates tumoricidal and bactericidal actions, as indicated by the fact that inhibitors of NO synthase (NOS) block these effects. Neuronal NOS and macrophage NOS are distinct isoforms.[3] Both the neuronal and the macrophage forms are unusual among oxidative enzymes in requiring several electron donors: FAD, flavin mononucleotide (FMN), NADPH, and tetrahydrobiopterin.[4]
Clinical significance
It has been implicated in asthma,[5][6] schizophrenia[7][8] and restless leg syndrome.[9] It has also been investigated with respect to bipolar disorder.[10]
Interactions
NOS1 has been shown to interact with DLG4[11][12] and NOS1AP.[11]
See also
References
- ^ Kishimoto J, Spurr N, Liao M, Lizhi L, Emson P, Xu W (November 1992). "Localization of brain nitric oxide synthase (NOS) to human chromosome 12". Genomics 14 (3): 802–4. doi:10.1016/S0888-7543(05)80192-2. PMID 1385308.
- ^ Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR (April 1993). "Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes". Proc. Natl. Acad. Sci. U.S.A. 90 (8): 3491–5. doi:10.1073/pnas.90.8.3491. PMC 46326. PMID 7682706. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46326.
- ^ Lowenstein CJ, Glatt CS, Bredt DS, Snyder SH (August 1992). "Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme". Proc. Natl. Acad. Sci. U.S.A. 89 (15): 6711–5. doi:10.1073/pnas.89.15.6711. PMC 49573. PMID 1379716. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49573.
- ^ "Entrez Gene: NOS1 Nitric oxide synthase 1 (neuronal)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4843.
- ^ Grasemann H, Yandava CN, Drazen JM (December 1999). "Neuronal NO synthase (NOS1) is a major candidate gene for asthma". Clin. Exp. Allergy. 29 Suppl 4: 39–41. PMID 10641565. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=1999&volume=29&issue=&spage=39.
- ^ Leung TF, Liu EK, Tang NL, Ko FW, Li CY, Lam CW, Wong GW (October 2005). "Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children". Clin. Exp. Allergy 35 (10): 1288–94. doi:10.1111/j.1365-2222.2005.02342.x. PMID 16238787.
- ^ Shinkai T, Ohmori O, Hori H, Nakamura J (2002). "Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia". Mol. Psychiatry 7 (6): 560–3. doi:10.1038/sj.mp.4001041. PMID 12140778.
- ^ Reif A, Herterich S, Strobel A, Ehlis AC, Saur D, Jacob CP, Wienker T, Töpner T, Fritzen S, Walter U, Schmitt A, Fallgatter AJ, Lesch KP (March 2006). "A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function". Mol. Psychiatry 11 (3): 286–300. doi:10.1038/sj.mp.4001779. PMID 16389274.
- ^ Winkelmann J, Lichtner P, Schormair B, Uhr M, Hauk S, Stiasny-Kolster K, Trenkwalder C, Paulus W, Peglau I, Eisensehr I, Illig T, Wichmann HE, Pfister H, Golic J, Bettecken T, Pütz B, Holsboer F, Meitinger T, Müller-Myhsok B (February 2008). "Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome". Mov. Disord. 23 (3): 350–8. doi:10.1002/mds.21647. PMID 18058820.
- ^ Buttenschön HN, Mors O, Ewald H, McQuillin A, Kalsi G, Lawrence J, Gurling H, Kruse TA (January 2004). "No association between a neuronal nitric oxide synthase (NOS1) gene polymorphism on chromosome 12q24 and bipolar disorder". Am. J. Med. Genet. B Neuropsychiatr. Genet. 124B (1): 73–5. doi:10.1002/ajmg.b.20040. PMID 14681919.
- ^ a b Jaffrey, S R; Snowman A M, Eliasson M J, Cohen N A, Snyder S H (Jan. 1998). "CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95". Neuron (UNITED STATES) 20 (1): 115–24. doi:10.1016/S0896-6273(00)80439-0. ISSN 0896-6273. PMID 9459447.
- ^ Brenman, J E; Chao D S, Gee S H, McGee A W, Craven S E, Santillano D R, Wu Z, Huang F, Xia H, Peters M F, Froehner S C, Bredt D S (Mar. 1996). "Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains". Cell (UNITED STATES) 84 (5): 757–67. doi:10.1016/S0092-8674(00)81053-3. ISSN 0092-8674. PMID 8625413.
Further reading
- Miyagoe-Suzuki Y, Takeda SI (2002). "Association of neuronal nitric oxide synthase (nNOS) with alpha1-syntrophin at the sarcolemma.". Microsc. Res. Tech. 55 (3): 164–70. doi:10.1002/jemt.1167. PMID 11747091.
- Waddington SN (2002). "Arginase in glomerulonephritis.". Kidney Int. 61 (3): 876–81. doi:10.1046/j.1523-1755.2002.00236.x. PMID 11849441.
- Rotilio G, Aquilano K, Ciriolo MR (2004). "Interplay of Cu,Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes.". IUBMB Life 55 (10-11): 629–34. doi:10.1080/15216540310001628717. PMID 14711010.
PDB gallery 1b8q: SOLUTION STRUCTURE OF THE EXTENDED NEURONAL NITRIC OXIDE SYNTHASE PDZ DOMAIN COMPLEXED WITH AN ASSOCIATED PEPTIDE1f20: CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE FAD/NADP+ DOMAIN AT 1.9A RESOLUTION.1k2r: Structure of rat brain nNOS heme domain complexed with NG-nitro-L-arginine1k2s: Structure of rat brain nNOS heme domain complexed with NG-allyl-L-arginine1k2t: Structure of rat brain nNOS heme domain complexed with S-ethyl-N-phenyl-isothiourea1k2u: Structure of rat brain nNOS heme domain complexed with S-ethyl-N-[4-(trifluoromethyl)phenyl] isothiourea1lzx: Rat neuronal NOS heme domain with NG-hydroxy-L-arginine bound1lzz: Rat neuronal NOS heme domain with N-isopropyl-N'-hydroxyguanidine bound1m00: Rat neuronal NOS heme domain with N-butyl-N'-hydroxyguanidine bound1mmv: Rat neuronal NOS heme domain with NG-propyl-L-arginine bound1mmw: Rat neuronal NOS heme domain with vinyl-L-NIO bound1om4: STRUCTURE OF RAT NEURONAL NOS HEME DOMAIN WITH L-ARGININE BOUND1om5: STRUCTURE OF RAT NEURONAL NOS HEME DOMAIN WITH 3-BROMO-7-NITROINDAZOLE BOUND1p6h: Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-2,4-L-diaminobutyric amide bound1p6i: Rat neuronal NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound1p6j: Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound1p6k: Rat neuronal NOS D597N mutant heme domain with L-N(omega)-nitroarginine-2,4-L-diaminobutyric amide bound1qau: UNEXPECTED MODES OF PDZ DOMAIN SCAFFOLDING REVEALED BY STRUCTURE OF NNOS-SYNTROPHIN COMPLEX1qav: Unexpected Modes of PDZ Domain Scaffolding Revealed by Structure of NNOS-Syntrophin Complex1qw6: Rat neuronal nitric oxide synthase oxygenase domain in complex with N-omega-propyl-L-Arg.1qwc: Rat neuronal nitric oxide synthase oxygenase domain in complex with W1400 inhibitor.1rs6: Rat neuronal NOS heme domain with D-lysine-D-nitroarginine amide bound1rs7: Rat neuronal NOS heme domain with D-phenylalanine-D-nitroarginine amide bound1tll: CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE REDUCTASE MODULE AT 2.3 A RESOLUTION.1vag: Neuronal nitric oxide synthase oxygenase domain complexed with the inhibitor AR-R174771zvi: Rat Neuronal Nitric Oxide Synthase Oxygenase Domain1zvl: Rat Neuronal Nitric Oxide Synthase Oxygenase Domain complexed with natural substrate L-Arg.1zzq: Rat nNOS D597N mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound1zzr: Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound1zzu: Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-2,4-L-Diaminobutyric Amide Bound2g6h: Structure of rat nNOS heme domain (BH4 bound) in the reduced form2g6i: Structure of rat nNOS heme domain (BH2-bound) in the reduced form2g6j: Structure of rat nNOS (L337N) heme domain (4-aminobiopterin bound) complexed with NO2g6k: Structure of rat nNOS heme domain (BH4 bound) complexed with NO2g6l: Structure of rat nNOS heme domain (BH2 bound) complexed with NO2g6m: Structure of rat nNOS heme domain (BH4 bound) complexed with CO2g6n: Strcture of rat nNOS heme domain (BH2 bound) complexed with CO2hx3: Rat nNOS heme domain complexed with (4S)-N-{4-Amino-5-[(2-aminoethyl)-hydroxyamino]-pentyl}-N'-nitroguanidine2hx4: Rat nNOS heme domain complexed with 4-N-(Nw-nitro-L-argininyl)-trans-4-hydroxyamino-L-proline amideThis article incorporates text from the United States National Library of Medicine, which is in the public domain.
Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14) 1.14.11: 2-oxoglutarate 1.14.13: NADH or NADPH Flavin-containing monooxygenase (FMO1, FMO2, FMO3, FMO4, FMO5) - Nitric oxide synthase (NOS1, NOS2, NOS3) - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 - Lanosterol 14 alpha-demethylase1.14.14: reduced flavin or flavoprotein 1.14.15: reduced iron-sulfur protein 1.14.16: reduced pteridine (BH4 dependent) 1.14.17: reduced ascorbate 1.14.18-19: other 1.14.99 - miscellaneous monoamine glutamate→GABAanabolism: Glutamate decarboxylase
catabolism: 4-aminobutyrate aminotransferase · 4-aminobutyrate transaminasearginine→NO choline→Acetylcholine anabolism: Choline acetyltransferase
catabolism: Cholinesterase (Acetylcholinesterase, Butyrylcholinesterase)Categories:- Human proteins
- Biology of bipolar disorder
- Chromosome 12 gene stubs
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