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PDBsum entry 1ed5
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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1ed5

 

 

 

 

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Contents
Protein chains
416 a.a. *
Ligands
ACT ×2
HEM ×2
NRG ×2
CAD ×2
GOL ×4
Metals
_ZN
Waters ×633
* Residue conservation analysis
PDB id:
1ed5
Name: Oxidoreductase
Title: Bovine endothelial nitric oxide synthase heme domain complexed with nna(h4b free)
Structure: Nitric oxide synthase. Chain: a, b. Fragment: heme domain (residues 39-482). Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Cell: endothelial. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.206     R-free:   0.238
Authors: C.S.Raman,H.Li,P.Martasek,G.J.Southan,B.S.S.Masters,T.L.Poulos
Key ref:
C.S.Raman et al. (2001). Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism. Biochemistry, 40, 13448-13455. PubMed id: 11695891 DOI: 10.1021/bi010957u
Date:
26-Jan-00     Release date:   31-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P29473  (NOS3_BOVIN) -  Nitric oxide synthase 3 from Bos taurus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1205 a.a.
416 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.14.13.39  - nitric-oxide synthase (NADPH).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 L-arginine + 3 NADPH + 4 O2 + H+ = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
2 × L-arginine
 +
3 × NADPH
Bound ligand (Het Group name = NRG)
matches with 80.00% similarity 		+ 4 × O2
 + H(+)
 = 2 × L-citrulline
 + 2 × nitric oxide
 + 3 × NADP(+)
 + 4 × H2O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi010957u Biochemistry 40:13448-13455 (2001)
PubMed id: 11695891  
 
 
Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism.
C.S.Raman, H.Li, P.Martásek, G.Southan, B.S.Masters, T.L.Poulos.
 
  ABSTRACT  
 
Nitric oxide is generated under normal and pathophysiological conditions by three distinct isoforms of nitric oxide synthase (NOS). A small-molecule inhibitor of NOS (3-Br-7-nitroindazole, 7-NIBr) is profoundly neuroprotective in mouse models of stroke and Parkinson's disease. We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution. Critical to the binding of 7-NIBr at the substrate site is the adoption by eNOS of an altered conformation, in which a key glutamate residue swings out toward one of the heme propionate groups. Perturbation of the heme propionate ensues and eliminates the cofactor tetrahydrobiopterin-heme interaction. We also present three crystal structures that reveal how alterations at the substrate site facilitate 7-NIBr and structurally dissimilar ligands to occupy the cofactor site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21482467 R.J.Young, W.Alderton, A.D.Angell, P.J.Beswick, D.Brown, C.L.Chambers, M.C.Crowe, J.Dawson, C.C.Hamlett, S.T.Hodgson, S.Kleanthous, R.G.Knowles, L.J.Russell, R.Stocker, and J.M.Woolven (2011).
Heteroalicyclic carboxamidines as inhibitors of inducible nitric oxide synthase; the identification of (2R)-2-pyrrolidinecarboxamidine as a potent and selective haem-co-ordinating inhibitor.
  Bioorg Med Chem Lett, 21, 3037-3040.  
19951943 C.Giroud, M.Moreau, T.A.Mattioli, V.Balland, J.L.Boucher, Y.Xu-Li, D.J.Stuehr, and J.Santolini (2010).
Role of arginine guanidinium moiety in nitric-oxide synthase mechanism of oxygen activation.
  J Biol Chem, 285, 7233-7245.  
16367758 D.Lefèvre-Groboillot, J.L.Boucher, D.Mansuy, and D.J.Stuehr (2006).
Reactivity of the heme-dioxygen complex of the inducible nitric oxide synthase in the presence of alternative substrates.
  FEBS J, 273, 180-191.  
15574418 A.J.Cardounel, Y.Xia, and J.L.Zweier (2005).
Endogenous methylarginines modulate superoxide as well as nitric oxide generation from neuronal nitric-oxide synthase: differences in the effects of monomethyl- and dimethylarginines in the presence and absence of tetrahydrobiopterin.
  J Biol Chem, 280, 7540-7549.  
15955074 D.Lefèvre-Groboillot, J.L.Boucher, D.J.Stuehr, and D.Mansuy (2005).
Relationship between the structure of guanidines and N-hydroxyguanidines, their binding to inducible nitric oxide synthase (iNOS) and their iNOS-catalysed oxidation to NO.
  FEBS J, 272, 3172-3183.  
15651036 S.B.Kirton, C.W.Murray, M.L.Verdonk, and R.D.Taylor (2005).
Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins.
  Proteins, 58, 836-844.  
15701046 S.Y.Proskuryakov, A.G.Konoplyannikov, V.G.Skvortsov, A.A.Mandrugin, and V.M.Fedoseev (2005).
Structure and activity of NO synthase inhibitors specific to the L-arginine binding site.
  Biochemistry (Mosc), 70, 8.  
15451052 D.Mansuy, and J.L.Boucher (2004).
Alternative nitric oxide-producing substrates for NO synthases.
  Free Radic Biol Med, 37, 1105-1121.  
14718923 M.L.Flinspach, H.Li, J.Jamal, W.Yang, H.Huang, J.M.Hah, J.A.Gómez-Vidal, E.A.Litzinger, R.B.Silverman, and T.L.Poulos (2004).
Structural basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase.
  Nat Struct Mol Biol, 11, 54-59.
PDB codes: 1p6h 1p6i 1p6j 1p6k 1p6l 1p6m 1p6n 1q2o
15004019 S.Marchal, A.C.Gorren, M.Sørlie, K.K.Andersson, B.Mayer, and R.Lange (2004).
Evidence of two distinct oxygen complexes of reduced endothelial nitric oxide synthase.
  J Biol Chem, 279, 19824-19831.  
12655056 J.T.Groves (2003).
The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies.
  Proc Natl Acad Sci U S A, 100, 3569-3574.  
12954642 R.Fedorov, E.Hartmann, D.K.Ghosh, and I.Schlichting (2003).
Structural basis for the specificity of the nitric-oxide synthase inhibitors W1400 and Nomega-propyl-L-Arg for the inducible and neuronal isoforms.
  J Biol Chem, 278, 45818-45825.
PDB codes: 1qw4 1qw5 1qw6 1qwc
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
12056914 A.C.Gorren, K.Schmidt, and B.Mayer (2002).
Binding of L-arginine and imidazole suggests heterogeneity of rat brain neuronal nitric oxide synthase.
  Biochemistry, 41, 7819-7829.  
12415184 J.Sopková-de Oliveira Santos, V.Collot, and S.Rault (2002).
7-Methoxy-1H-indazole, a new inhibitor of neuronal nitric oxide synthase.
  Acta Crystallogr C, 58, o688-o690.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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