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Neuronal NOS

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Target not currently curated in GtoImmuPdb

Target id: 1251

Nomenclature: Neuronal NOS

Abbreviated Name: nNOS

Family: Nitric oxide synthases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1434 12q24.22 NOS1 nitric oxide synthase 1
Mouse - 1429 5 57.29 cM Nos1 nitric oxide synthase 1, neuronal
Rat - 1429 12q16 Nos1 nitric oxide synthase 1
Previous and Unofficial Names Click here for help
brain NOS | NOS1 | constitutive NOS | NC-NOS | neuronal NOS | nitric oxide synthase 1 | Nitric oxide synthase 1 (neuronal) | Nitric oxide synthase 1 / NOSI | nitric oxide synthase 1 (neuronal)
Database Links Click here for help
Alphafold P29475 (Hs), Q9Z0J4 (Mm), P29476 (Rn)
BRENDA 1.14.13.39
CATH/Gene3D 3.40.50.360
ChEMBL Target CHEMBL3568 (Hs), CHEMBL4719 (Mm), CHEMBL3048 (Rn)
Ensembl Gene ENSG00000089250 (Hs), ENSMUSG00000029361 (Mm), ENSRNOG00000001130 (Rn)
Entrez Gene 4842 (Hs), 18125 (Mm), 24598 (Rn)
Human Protein Atlas ENSG00000089250 (Hs)
KEGG Enzyme 1.14.13.39
KEGG Gene hsa:4842 (Hs), mmu:18125 (Mm), rno:24598 (Rn)
OMIM 163731 (Hs)
Pharos P29475 (Hs)
SynPHARM 83559 (in complex with compound 14j [PMID: 27050842])
83560 (in complex with compound 14j [PMID: 27050842])
78396 (in complex with Nωpropyl-L-arginine)
UniProtKB P29475 (Hs), Q9Z0J4 (Mm), P29476 (Rn)
Wikipedia NOS1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of rat neuronal nitric oxide synthase heme domain in complex with 4-methyl-6-(2-(5-(3-(methylamino)propyl)pyridin-3-yl) ethyl)pyridin-2-amine
PDB Id:  5FVS
Ligand:  compound 14j [PMID: 27050842]
Resolution:  1.95Å
Species:  Rat
References:  5
Enzyme Reaction Click here for help
EC Number: 1.14.13.39
Products Click here for help
Product Species Reference
NO Human
L-citrulline Human
Cofactors Click here for help
Cofactor Species Comments Reference
Zn2+ Human
NADPH Human
heme Human
flavin adenine dinucleotide Human
flavin mononucleotide Human
BH4 Human
oxygen Human
Endogenous Substrate (Human)
L-arginine

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 14j [PMID: 27050842] Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.9 pKi 5
⤷ pKi 7.9 (Ki 1.3x10-8 M) [5]
L-NNA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pKi 1
⤷ pKi 7.8 (Ki 1.5x10-8 M) [1]
compound 14j [PMID: 27050842] Small molecule or natural product Ligand has a PDB structure Rn Inhibition 7.8 pKi 5
⤷ pKi 7.8 (Ki 1.6x10-8 M) [5]
Nωpropyl-L-arginine Small molecule or natural product Rn Inhibition 7.2 pKi 6
⤷ pKi 7.2 [6]
tilarginine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pKi 3
⤷ pKi 6.1 (Ki 8.4x10-7 M) [3]
GW274150 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 4.7 pIC50 2
⤷ pIC50 4.7 (IC50 1.8x10-5 M) [2]
NANT Small molecule or natural product Ligand has a PDB structure N/A Inhibition - -
⤷
View species-specific inhibitor tables
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ZZL-7 Peptide Hs Binding - - 4
⤷ [4]

References

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1. Collins JL, Shearer BG, Oplinger JA, Lee S, Garvey EP, Salter M, Duffy C, Burnette TC, Furfine ES. (1998) N-Phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity. J Med Chem, 41 (15): 2858-71. [PMID:9667974]

2. Connolly S, Aberg A, Arvai A, Beaton HG, Cheshire DR, Cook AR, Cooper S, Cox D, Hamley P, Mallinder P et al.. (2004) 2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution. J Med Chem, 47 (12): 3320-3. [PMID:15163211]

3. Shearer BG, Lee S, Franzmann KW, White HA, Sanders DC, Kiff RJ, Garvey EP, Furfine ES. (1997) Conformationally restricted arginine analogues as inhibitors of human nitric oxide synthase. Bioorganic and Medicinal Chemistry Letters, 7: 1763-1768. DOI: 10.1016/S0960-894X(97)00309-0

4. Sun N, Qin YJ, Xu C, Xia T, Du ZW, Zheng LP, Li AA, Meng F, Zhang Y, Zhang J et al.. (2022) Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN. Science, 378 (6618): 390-398. [PMID:36302033]

5. Wang HY, Qin Y, Li H, Roman LJ, Martásek P, Poulos TL, Silverman RB. (2016) Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker. J Med Chem, 59 (10): 4913-25. [PMID:27050842]

6. Zhang HQ, Fast W, Marletta MA, Martasek P, Silverman RB. (1997) Potent and selective inhibition of neuronal nitric oxide synthase by N omega-propyl-L-arginine. J Med Chem, 40 (24): 3869-70. [PMID:9397167]

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