PDBsum entry 3jwu

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
407 a.a. *
HEM ×2
H4B ×2
J11 ×2
ACT ×2
Waters ×391
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Structure of rat neuronal nitric oxide synthase r349a mutant domain in complex with n1-{(3'r,4's)-4'-[(6"-amino-4"-methy 2"-yl)methyl]pyrrolidin-3'-yl}-n2-(3'-fluorophenethyl)ethan diamine tetrahydrochloride
Structure: Nitric oxide synthase, brain. Chain: a, b. Fragment: residues 297-718. Synonym: bnos, nos type i, neuronal nos, n-nos, nnos, const nos, nc-nos. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: nos1, bnos. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.93Å     R-factor:   0.182     R-free:   0.205
Authors: S.L.Delker,H.Li,T.L.Poulos
Key ref: S.L.Delker et al. (2010). Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of a cerebral palsy phenotype in an animal model. J Am Chem Soc, 132, 5437-5442. PubMed id: 20337441
18-Sep-09     Release date:   05-May-10    
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Protein chains
Pfam   ArchSchema ?
P29476  (NOS1_RAT) -  Nitric oxide synthase, brain
1429 a.a.
407 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Nitric-oxide synthase (Nadph dependent).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
2 × L-arginine
+ 3 × NADPH
+ 4 × O(2)
= 2 × L-citrulline
+ 2 × nitric oxide
+ 3 × NADP(+)
+ 4 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     nitric-oxide synthase activity     1 term  


J Am Chem Soc 132:5437-5442 (2010)
PubMed id: 20337441  
Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of a cerebral palsy phenotype in an animal model.
S.L.Delker, H.Ji, H.Li, J.Jamal, J.Fang, F.Xue, R.B.Silverman, T.L.Poulos.
Selective inhibition of the neuronal isoform of nitric oxide synthase NOS (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. However, given the high active site conservation among all three NOS isoforms, the design of selective inhibitors is an extremely challenging problem. Here we present the structural basis for why novel and potent nNOS inhibitors exhibit the highest level of selectivity over eNOS reported so far (approximately 3,800-fold). By using a combination of crystallography, computational methods, and site-directed mutagenesis, we found that inhibitor chirality and an unanticipated structural change of the target enzyme control both the orientation and selectivity of these novel nNOS inhibitors. A new hot spot generated as a result of enzyme elasticity provides important information for the future fragment-based design of selective NOS inhibitors.