Function and Biology

Structure of rat neuronal nitric oxide synthase in complex with 6,6'-((5-(aminomethyl)-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)

Source organism: Rattus norvegicus
Biochemical function: nitric-oxide synthase activity
Biological process: nitric oxide biosynthetic process
Cellular component: not assigned

EC 1.14.13.39: Nitric-oxide synthase (NADPH)

Reaction catalysed:
2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O.
Comments:
  • The enzyme consists of linked oxygenase and reductase domains.
  • The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains are linked via a regulatory calmodulin-binding domain.
  • Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center.
  • The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center.
  • Cf. EC 1.14.14.47.
Systematic name:
L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)
Alternative Name(s):
  • NADPH-diaphorase
  • NO synthase
  • Endothelium-derived relaxation factor-forming enzyme
  • Endothelium-derived relaxing factor synthase
  • Nitric oxide synthetase
  • Nitric-oxide synthetase
  • NOS (gene name)

GO terms

Biochemical function:
Biological process:
Cellular component:
  • not assigned

Sequence family

CATH Protein family (Pfam)
PF02898
Domain description: Nitric oxide synthase, oxygenase domain
Occurring in:
  1. Nitric oxide synthase, brain
1 copy of Pfam domain PF02898 (Nitric oxide synthase, oxygenase domain) in Nitric oxide synthase, brain in PDB 4imu.

CATH InterPro annotation
IPR004030
Domain description: Nitric oxide synthase, N-terminal
Occurring in:
  1. Nitric oxide synthase, brain

Structure domains

CATH CATH domains
3.90.340.10
Class: Alpha Beta
Architecture: Alpha-Beta Complex
Topology: Nitric Oxide Synthase; Chain A, domain 1
Homology: Nitric Oxide Synthase; Chain A, domain 1
Occurring in:
  1. Nitric oxide synthase, brain
1 copy of CATH domain 3.90.340.10 (Nitric Oxide Synthase; Chain A, domain 1) in Nitric oxide synthase, brain in PDB 4imu.
3.90.440.10
Class: Alpha Beta
Architecture: Alpha-Beta Complex
Topology: Nitric Oxide Synthase;Heme Domain; Chain A, domain 2
Homology: Nitric Oxide Synthase;Heme Domain;Chain A domain 2
Occurring in:
  1. Nitric oxide synthase, brain
1 copy of CATH domain 3.90.440.10 (Nitric Oxide Synthase;Heme Domain; Chain A, domain 2) in Nitric oxide synthase, brain in PDB 4imu.