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PDBsum entry 4nos
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Oxidoreductase PDB id
4nos

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
421 a.a. *
Ligands
HEM ×4
H2B
ITU ×4
H4B ×3
Metals
_ZN ×2
Waters ×1371
* Residue conservation analysis
PDB id:
4nos
Name: Oxidoreductase
Title: Human inducible nitric oxide synthase with inhibitor
Structure: Inducible nitric oxide synthase. Chain: a, b, c, d. Fragment: oxygenase domain. Synonym: inos, nos2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.25Å     R-factor:   0.199     R-free:   0.289
Authors: T.O.Fischmann,P.C.Weber
Key ref:
T.O.Fischmann et al. (1999). Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol, 6, 233-242. PubMed id: 10074942 DOI: 10.1038/6675
Date:
03-Feb-99     Release date:   04-Feb-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P35228  (NOS2_HUMAN) -  Nitric oxide synthase, inducible from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1153 a.a.
421 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
 + 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: 10.1038/6675 Nat Struct Biol 6:233-242 (1999)
PubMed id: 10074942  
 
 
Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation.
T.O.Fischmann, A.Hruza, X.D.Niu, J.D.Fossetta, C.A.Lunn, E.Dolphin, A.J.Prongay, P.Reichert, D.J.Lundell, S.K.Narula, P.C.Weber.
 
  ABSTRACT  
 
Crystal structures of human endothelial nitric oxide synthase (eNOS) and human inducible NOS (iNOS) catalytic domains were solved in complex with the arginine substrate and an inhibitor S-ethylisothiourea (SEITU), respectively. The small molecules bind in a narrow cleft within the larger active-site cavity containing heme and tetrahydrobiopterin. Both are hydrogen-bonded to a conserved glutamate (eNOS E361, iNOS E377). The active-site residues of iNOS and eNOS are nearly identical. Nevertheless, structural comparisons provide a basis for design of isozyme-selective inhibitors. The high-resolution, refined structures of eNOS (2.4 A resolution) and iNOS (2.25 A resolution) reveal an unexpected structural zinc situated at the intermolecular interface and coordinated by four cysteines, two from each monomer.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Electron density maps in the immediate vicinity of the zinc (a,b ) or BH[4] (c,d), contoured at 1.2 (green) and 3.6 (purple). (Left panels) Experimental electron density maps after density modification. (Right panels) 2(F[obs] -F[calc]) electron density maps after refinement. The final model in a ball-and-stick representation is superposed on the maps. a,b Electron density maps in the immediate vicinity of the zinc for iNOS[ox] and eNOS[ox], respectively. The maps clearly define the zinc atom and its coordination. Model colors and orientation as in Fig. 6. c,d Electron density maps in the immediate vicinity of BH[4], iNOS[ox] and eNOS[ox], respectively. All figures were generated using MOLSCRIPT^40 and RASTER3D^41. 		Figure 2.
Figure 2. Structures of a, eNOS[ox] and b, iNOS[ ox] monomers shown as ribbon diagrams, along with heme, BH[4] and either the arginine substrate for eNOS[ox] or the inhibitor SEITU for iNOS[ox], drawn in a ball-and-stick representation. Both structures are in a similar orientation In this view, the heme propionate groups are facing away from the viewer BH[4] is located farther down the cavity and the cavity entrance is on the opposite side of the monomer. The colors are consistent with Fig. 3. (a) eNOS[ ox] colored according to each subdomain. (b) iNOSox painted with the Hue Saturation Brightness color wheel starting with magenta at the N-terminal residue to red at the C-terminus.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 233-242) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference Google scholar

  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.
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20840589 A.Maréchal, T.A.Mattioli, D.J.Stuehr, and J.Santolini (2010).
NO synthase isoforms specifically modify peroxynitrite reactivity.
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20370423 B.R.Crane, J.Sudhamsu, and B.A.Patel (2010).
Bacterial nitric oxide synthases.
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20226211 D.Schade, J.Kotthaus, and B.Clement (2010).
Modulating the NO generating system from a medicinal chemistry perspective: current trends and therapeutic options in cardiovascular disease.
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20184449 F.V.Fonseca, K.Ravi, D.Wiseman, M.Tummala, C.Harmon, V.Ryzhov, J.R.Fineman, and S.M.Black (2010).
Mass spectroscopy and molecular modeling predict endothelial nitric oxide synthase dimer collapse by hydrogen peroxide through zinc tetrathiolate metal-binding site disruption.
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20184376 W.Chen, L.J.Druhan, C.A.Chen, C.Hemann, Y.R.Chen, V.Berka, A.L.Tsai, and J.L.Zweier (2010).
Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition.
  Biochemistry, 49, 3129-3137.  
19081984 B.L.Oliveira, J.D.Correia, P.D.Raposinho, I.Santos, A.Ferreira, C.Cordeiro, and A.P.Freire (2009).
Re and (99m)Tc organometallic complexes containing pendant l-arginine derivatives as potential probes of inducible nitric oxide synthase.
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19398561 B.S.Masters, and B.S.Masters (2009).
A professional and personal odyssey.
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19737939 C.Xia, I.Misra, T.Iyanagi, and J.J.Kim (2009).
Regulation of interdomain interactions by calmodulin in inducible nitric-oxide synthase.
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19583767 D.J.Stuehr, J.Tejero, and M.M.Haque (2009).
Structural and mechanistic aspects of flavoproteins: electron transfer through the nitric oxide synthase flavoprotein domain.
  FEBS J, 276, 3959-3974.  
19125620 H.Ji, H.Li, P.Martásek, L.J.Roman, T.L.Poulos, and R.B.Silverman (2009).
Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping.
  J Med Chem, 52, 779-797.  
19146393 H.Ouellet, J.Lang, M.Couture, and P.R.Ortiz de Montellano (2009).
Reaction of Mycobacterium tuberculosis cytochrome P450 enzymes with nitric oxide.
  Biochemistry, 48, 863-872.  
19358819 P.F.Chen, and K.K.Wu (2009).
Two synthetic peptides corresponding to the proximal heme-binding domain and CD1 domain of human endothelial nitric-oxide synthase inhibit the oxygenase activity by interacting with CaM.
  Arch Biochem Biophys, 486, 132-140.  
19154146 R.B.Silverman (2009).
Design of selective neuronal nitric oxide synthase inhibitors for the prevention and treatment of neurodegenerative diseases.
  Acc Chem Res, 42, 439-451.  
19046139 S.Messner, S.Leitner, C.Bommassar, G.Golderer, P.Gröbner, E.R.Werner, and G.Werner-Felmayer (2009).
Physarum nitric oxide synthases: genomic structures and enzymology of recombinant proteins.
  Biochem J, 418, 691-700.  
19805284 T.Agapie, S.Suseno, J.J.Woodward, S.Stoll, R.D.Britt, and M.A.Marletta (2009).
NO formation by a catalytically self-sufficient bacterial nitric oxide synthase from Sorangium cellulosum.
  Proc Natl Acad Sci U S A, 106, 16221-16226.  
18056997 C.Metcalfe, I.K.Macdonald, E.J.Murphy, K.A.Brown, E.L.Raven, and P.C.Moody (2008).
The tuberculosis prodrug isoniazid bound to activating peroxidases.
  J Biol Chem, 283, 6193-6200.
PDB codes: 2v23 2v2e 2vcf 2vcn 2vcs
18849972 E.D.Garcin, A.S.Arvai, R.J.Rosenfeld, M.D.Kroeger, B.R.Crane, G.Andersson, G.Andrews, P.J.Hamley, P.R.Mallinder, D.J.Nicholls, S.A.St-Gallay, A.C.Tinker, N.P.Gensmantel, A.Mete, D.R.Cheshire, S.Connolly, D.J.Stuehr, A.Aberg, A.V.Wallace, J.A.Tainer, and E.D.Getzoff (2008).
Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.
  Nat Chem Biol, 4, 700-707.
PDB codes: 3e65 3e67 3e68 3e6l 3e6n 3e6o 3e6t 3e7g 3e7i 3e7m 3e7s 3e7t 3eah 3eai 3ebd 3ebf 3ej8
18815130 J.Tejero, A.Biswas, Z.Q.Wang, R.C.Page, M.M.Haque, C.Hemann, J.L.Zweier, S.Misra, and D.J.Stuehr (2008).
Stabilization and Characterization of a Heme-Oxy Reaction Intermediate in Inducible Nitric-oxide Synthase.
  J Biol Chem, 283, 33498-33507.
PDB code: 3dwj
18193303 S.M.Francis, A.Mittal, M.Sharma, and P.V.Bharatam (2008).
Design of benzene-1,2-diamines as selective inducible nitric oxide synthase inhibitors: a combined de novo design and docking analysis.
  J Mol Model, 14, 215-224.  
18954462 T.A.Binkowski, and A.Joachimiak (2008).
Protein functional surfaces: global shape matching and local spatial alignments of ligand binding sites.
  BMC Struct Biol, 8, 45.  
17369257 A.Maréchal, T.A.Mattioli, D.J.Stuehr, and J.Santolini (2007).
Activation of peroxynitrite by inducible nitric-oxide synthase: a direct source of nitrative stress.
  J Biol Chem, 282, 14101-14112.  
18836533 C.Wheatley (2007).
The return of the Scarlet Pimpernel: cobalamin in inflammation II - cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS.
  J Nutr Environ Med, 16, 181-211.  
18923642 C.Wheatley (2007).
Cobalamin in inflammation III - glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: the sword in the stone? How cobalamin may directly regulate the nitric oxide synthases.
  J Nutr Environ Med, 16, 212-226.  
17614291 E.P.Erdal, P.Martásek, L.J.Roman, and R.B.Silverman (2007).
Hydroxyethylene isosteres of selective neuronal nitric oxide synthase inhibitors.
  Bioorg Med Chem, 15, 6096-6108.  
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
17534534 S.Schneider, J.Marles-Wright, K.H.Sharp, and M.Paoli (2007).
Diversity and conservation of interactions for binding heme in b-type heme proteins.
  Nat Prod Rep, 24, 621-630.  
17534526 T.L.Poulos (2007).
The Janus nature of heme.
  Nat Prod Rep, 24, 504-510.  
16461329 D.K.Ghosh, M.A.Holliday, C.Thomas, J.B.Weinberg, S.M.Smith, and J.C.Salerno (2006).
Nitric-oxide synthase output state. Design and properties of nitric-oxide synthase oxygenase/FMN domain constructs.
  J Biol Chem, 281, 14173-14183.  
16421101 D.Li, E.Y.Hayden, K.Panda, D.J.Stuehr, H.Deng, D.L.Rousseau, and S.R.Yeh (2006).
Regulation of the monomer-dimer equilibrium in inducible nitric-oxide synthase by nitric oxide.
  J Biol Chem, 281, 8197-8204.  
17034131 H.Ji, J.A.Gómez-Vidal, P.Martasek, L.J.Roman, and R.B.Silverman (2006).
Conformationally restricted dipeptide amides as potent and selective neuronal nitric oxide synthase inhibitors.
  J Med Chem, 49, 6254-6263.  
16116474 P.Hausel, H.Latado, F.Courjault-Gautier, and E.Felley-Bosco (2006).
Src-mediated phosphorylation regulates subcellular distribution and activity of human inducible nitric oxide synthase.
  Oncogene, 25, 198-206.  
16411020 R.Sengupta, R.Sahoo, S.S.Ray, T.Dutta, A.Dasgupta, and S.Ghosh (2006).
Dissociation and unfolding of inducible nitric oxide synthase oxygenase domain identifies structural role of tetrahydrobiopterin in modulating the heme environment.
  Mol Cell Biochem, 284, 117-126.  
16966328 S.P.Panda, Y.T.Gao, L.J.Roman, P.Martásek, J.C.Salerno, and B.S.Masters (2006).
The role of a conserved serine residue within hydrogen bonding distance of FAD in redox properties and the modulation of catalysis by Ca2+/calmodulin of constitutive nitric-oxide synthases.
  J Biol Chem, 281, 34246-34257.  
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.  
15632185 C.C.Wei, Z.Q.Wang, D.Durra, C.Hemann, R.Hille, E.D.Garcin, E.D.Getzoff, and D.J.Stuehr (2005).
The three nitric-oxide synthases differ in their kinetics of tetrahydrobiopterin radical formation, heme-dioxy reduction, and arginine hydroxylation.
  J Biol Chem, 280, 8929-8935.  
16234921 D.J.Stuehr, C.C.Wei, Z.Wang, and R.Hille (2005).
Exploring the redox reactions between heme and tetrahydrobiopterin in the nitric oxide synthases.
  Dalton Trans, (), 3427-3435.  
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.  
15954154 H.Yin, and A.D.Hamilton (2005).
Strategies for targeting protein-protein interactions with synthetic agents.
  Angew Chem Int Ed Engl, 44, 4130-4163.  
16240674 M.Ghayour-Mobarhan, D.J.Lamb, A.Taylor, N.Vaidya, C.Livingstone, T.Wang, and G.A.Ferns (2005).
Effect of statin therapy on serum trace element status in dyslipidaemic subjects.
  J Trace Elem Med Biol, 19, 61-67.  
16249336 M.Jáchymová, P.Martásek, S.Panda, L.J.Roman, M.Panda, T.M.Shea, Y.Ishimura, J.J.Kim, and B.S.Masters (2005).
Recruitment of governing elements for electron transfer in the nitric oxide synthase family.
  Proc Natl Acad Sci U S A, 102, 15833-15838.  
16133202 M.L.Fernández, M.A.Martí, A.Crespo, and D.A.Estrin (2005).
Proximal effects in the modulation of nitric oxide synthase reactivity: a QM-MM study.
  J Biol Inorg Chem, 10, 595-604.  
16034613 S.Cai, J.Khoo, S.Mussa, N.J.Alp, and K.M.Channon (2005).
Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation.
  Diabetologia, 48, 1933-1940.  
16362154 S.Horie (2005).
ADPKD: molecular characterization and quest for treatment.
  Clin Exp Nephrol, 9, 282-291.  
15377396 A.K.Hesse, M.Dörger, C.Kupatt, and F.Krombach (2004).
Proinflammatory role of inducible nitric oxide synthase in acute hyperoxic lung injury.
  Respir Res, 5, 11.  
14594819 C.Gautier, M.Négrerie, Z.Q.Wang, J.C.Lambry, D.J.Stuehr, F.Collin, J.L.Martin, and A.Slama-Schwok (2004).
Dynamic regulation of the inducible nitric-oxide synthase by NO: comparison with the endothelial isoform.
  J Biol Chem, 279, 4358-4365.  
15608562 D.M.McDonald, N.J.Alp, and K.M.Channon (2004).
Functional comparison of the endothelial nitric oxide synthase Glu298Asp polymorphic variants in human endothelial cells.
  Pharmacogenetics, 14, 831-839.  
15451052 D.Mansuy, and J.L.Boucher (2004).
Alternative nitric oxide-producing substrates for NO synthases.
  Free Radic Biol Med, 37, 1105-1121.  
15572774 E.Blanc, P.Roversi, C.Vonrhein, C.Flensburg, S.M.Lea, and G.Bricogne (2004).
Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.
  Acta Crystallogr D Biol Crystallogr, 60, 2210-2221.  
15208315 E.D.Garcin, C.M.Bruns, S.J.Lloyd, D.J.Hosfield, M.Tiso, R.Gachhui, D.J.Stuehr, J.A.Tainer, and E.D.Getzoff (2004).
Structural basis for isozyme-specific regulation of electron transfer in nitric-oxide synthase.
  J Biol Chem, 279, 37918-37927.
PDB code: 1tll
15224385 H.Matter, and P.Kotsonis (2004).
Biology and chemistry of the inhibition of nitric oxide synthases by pteridine-derivatives as therapeutic agents.
  Med Res Rev, 24, 662-684.  
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
15189165 O.Pylypenko, and I.Schlichting (2004).
Structural aspects of ligand binding to and electron transfer in bacterial and fungal P450s.
  Annu Rev Biochem, 73, 991.  
15560776 P.Hlavica (2004).
Models and mechanisms of O-O bond activation by cytochrome P450. A critical assessment of the potential role of multiple active intermediates in oxidative catalysis.
  Eur J Biochem, 271, 4335-4360.  
15071192 R.Fedorov, R.Vasan, D.K.Ghosh, and I.Schlichting (2004).
Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design.
  Proc Natl Acad Sci U S A, 101, 5892-5897.
PDB codes: 1vaf 1vag
15166218 V.Berka, G.Wu, H.C.Yeh, G.Palmer, and A.L.Tsai (2004).
Three different oxygen-induced radical species in endothelial nitric-oxide synthase oxygenase domain under regulation by L-arginine and tetrahydrobiopterin.
  J Biol Chem, 279, 32243-32251.  
15256486 Y.Stasiv, B.Kuzin, M.Regulski, T.Tully, and G.Enikolopov (2004).
Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling.
  Genes Dev, 18, 1812-1823.  
14976216 Z.Q.Wang, C.C.Wei, M.Sharma, K.Pant, B.R.Crane, and D.J.Stuehr (2004).
A conserved Val to Ile switch near the heme pocket of animal and bacterial nitric-oxide synthases helps determine their distinct catalytic profiles.
  J Biol Chem, 279, 19018-19025.  
14504282 C.C.Wei, Z.Q.Wang, C.Hemann, R.Hille, and D.J.Stuehr (2003).
A tetrahydrobiopterin radical forms and then becomes reduced during Nomega-hydroxyarginine oxidation by nitric-oxide synthase.
  J Biol Chem, 278, 46668-46673.  
12805387 G.M.Knudsen, C.R.Nishida, S.D.Mooney, and P.R.Ortiz de Montellano (2003).
Nitric-oxide synthase (NOS) reductase domain models suggest a new control element in endothelial NOS that attenuates calmodulin-dependent activity.
  J Biol Chem, 278, 31814-31824.  
12847099 K.Panda, S.Adak, K.S.Aulak, J.Santolini, J.F.McDonald, and D.J.Stuehr (2003).
Distinct influence of N-terminal elements on neuronal nitric-oxide synthase structure and catalysis.
  J Biol Chem, 278, 37122-37131.  
12960153 L.E.Bretscher, H.Li, T.L.Poulos, and O.W.Griffith (2003).
Structural characterization and kinetics of nitric-oxide synthase inhibition by novel N5-(iminoalkyl)- and N5-(iminoalkenyl)-ornithines.
  J Biol Chem, 278, 46789-46797.
PDB codes: 1mmv 1mmw
12730215 L.J.Roman, J.McLain, and B.S.Masters (2003).
Chimeric enzymes of cytochrome P450 oxidoreductase and neuronal nitric-oxide synthase reductase domain reveal structural and functional differences.
  J Biol Chem, 278, 25700-25707.  
12480940 M.Du, H.C.Yeh, V.Berka, L.H.Wang, and A.L.Tsai (2003).
Redox properties of human endothelial nitric-oxide synthase oxygenase and reductase domains purified from yeast expression system.
  J Biol Chem, 278, 6002-6011.  
14561757 P.F.Chen, and K.K.Wu (2003).
Structural elements contribute to the calcium/calmodulin dependence on enzyme activation in human endothelial nitric-oxide synthase.
  J Biol Chem, 278, 52392-52400.  
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
14510776 W.Zhang, T.Kuncewicz, Z.Y.Yu, L.Zou, X.Xu, and B.C.Kone (2003).
Protein-protein interactions involving inducible nitric oxide synthase.
  Acta Physiol Scand, 179, 137-142.  
12777376 Z.W.Guan, D.Kamatani, S.Kimura, and T.Iyanagi (2003).
Mechanistic studies on the intramolecular one-electron transfer between the two flavins in the human neuronal nitric-oxide synthase and inducible nitric-oxide synthase flavin domains.
  J Biol Chem, 278, 30859-30868.  
11876653 A.R.Hurshman, and M.A.Marletta (2002).
Reactions catalyzed by the heme domain of inducible nitric oxide synthase: evidence for the involvement of tetrahydrobiopterin in electron transfer.
  Biochemistry, 41, 3439-3456.  
11719512 A.Slama-Schwok, M.Négrerie, V.Berka, J.C.Lambry, A.L.Tsai, M.H.Vos, and J.L.Martin (2002).
Nitric oxide (NO) traffic in endothelial NO synthase. Evidence for a new NO binding site dependent on tetrahydrobiopterin?
  J Biol Chem, 277, 7581-7586.  
11784303 J.Doyle, L.E.Llewellyn, C.S.Brinkworth, J.H.Bowie, K.L.Wegener, T.Rozek, P.A.Wabnitz, J.C.Wallace, and M.J.Tyler (2002).
Amphibian peptides that inhibit neuronal nitric oxide synthase. Isolation of lesuerin from the skin secretion of the Australian Stony Creek frog Litoria lesueuri.
  Eur J Biochem, 269, 100-109.  
11980473 J.P.Schelvis, V.Berka, G.T.Babcock, and A.L.Tsai (2002).
Resonance Raman detection of the Fe-S bond in endothelial nitric oxide synthase.
  Biochemistry, 41, 5695-5701.  
  12076969 K.K.Wu (2002).
Regulation of endothelial nitric oxide synthase activity and gene expression.
  Ann N Y Acad Sci, 962, 122-130.  
12048205 K.Panda, R.J.Rosenfeld, S.Ghosh, A.L.Meade, E.D.Getzoff, and D.J.Stuehr (2002).
Distinct dimer interaction and regulation in nitric-oxide synthase types I, II, and III.
  J Biol Chem, 277, 31020-31030.  
12220171 K.Pant, A.M.Bilwes, S.Adak, D.J.Stuehr, and B.R.Crane (2002).
Structure of a nitric oxide synthase heme protein from Bacillus subtilis.
  Biochemistry, 41, 11071-11079.
PDB codes: 1m7v 1m7z
11846789 P.Ascenzi, M.Fasano, M.Marino, G.Venturini, and R.Federico (2002).
Agmatine oxidation by copper amine oxidase.
  Eur J Biochem, 269, 884-892.  
11756668 S.Adak, A.M.Bilwes, K.Panda, D.Hosfield, K.S.Aulak, J.F.McDonald, J.A.Tainer, E.D.Getzoff, B.R.Crane, and D.J.Stuehr (2002).
Cloning, expression, and characterization of a nitric oxide synthase protein from Deinococcus radiodurans.
  Proc Natl Acad Sci U S A, 99, 107-112.  
12359874 S.Adak, M.Sharma, A.L.Meade, and D.J.Stuehr (2002).
A conserved flavin-shielding residue regulates NO synthase electron transfer and nicotinamide coenzyme specificity.
  Proc Natl Acad Sci U S A, 99, 13516-13521.  
12081486 W.J.Ingledew, S.M.Smith, J.C.Salerno, and P.R.Rich (2002).
Neuronal nitric oxide synthase ligand and protein vibrations at the substrate binding site. A study by FTIR.
  Biochemistry, 41, 8377-8384.  
11823464 Z.Q.Wang, C.C.Wei, and D.J.Stuehr (2002).
A conserved tryptophan 457 modulates the kinetics and extent of N-hydroxy-L-arginine oxidation by inducible nitric-oxide synthase.
  J Biol Chem, 277, 12830-12837.  
11358872 G.Golderer, E.R.Werner, S.Leitner, P.Gröbner, and G.Werner-Felmayer (2001).
Nitric oxide synthase is induced in sporulation of Physarum polycephalum.
  Genes Dev, 15, 1299-1309.  
11389602 H.M.Abu-Soud, K.Ichimori, H.Nakazawa, and D.J.Stuehr (2001).
Regulation of inducible nitric oxide synthase by self-generated NO.
  Biochemistry, 40, 6876-6881.  
11309260 J.M.Park, T.Higuchi, K.Kikuchi, Y.Urano, H.Hori, T.Nishino, J.Aoki, K.Inoue, and T.Nagano (2001).
Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides.
  Br J Pharmacol, 132, 1876-1882.  
11518705 K.Kobayashi, S.Tagawa, S.Daff, I.Sagami, and T.Shimizu (2001).
Rapid calmodulin-dependent interdomain electron transfer in neuronal nitric-oxide synthase measured by pulse radiolysis.
  J Biol Chem, 276, 39864-39871.  
11212498 M.David-Dufilho, C.Privat, A.Brunet, M.J.Richard, J.Devynck, and M.A.Devynck (2001).
[Transition metals and nitric oxide production in human endothelial cells].
  C R Acad Sci III, 324, 13-21.  
11298374 T.J.Guzik, E.Black, N.E.West, D.McDonald, C.Ratnatunga, R.Pillai, and K.M.Channon (2001).
Relationship between the G894T polymorphism (Glu298Asp variant) in endothelial nitric oxide synthase and nitric oxide-mediated endothelial function in human atherosclerosis.
  Am J Med Genet, 100, 130-137.  
10975456 A.W.Munro, P.Taylor, and M.D.Walkinshaw (2000).
Structures of redox enzymes.
  Curr Opin Biotechnol, 11, 369-376.  
10769116 B.R.Crane, A.S.Arvai, S.Ghosh, E.D.Getzoff, D.J.Stuehr, and J.A.Tainer (2000).
Structures of the N(omega)-hydroxy-L-arginine complex of inducible nitric oxide synthase oxygenase dimer with active and inactive pterins.
  Biochemistry, 39, 4608-4621.
PDB codes: 1dwv 1dww 1dwx
10956005 C.Jung, D.J.Stuehr, and D.K.Ghosh (2000).
FT-Infrared spectroscopic studies of the iron ligand CO stretch mode of iNOS oxygenase domain: effect of arginine and tetrahydrobiopterin.
  Biochemistry, 39, 10163-10171.  
10889028 C.Moali, M.Brollo, J.Custot, M.A.Sari, J.L.Boucher, D.J.Stuehr, and D.Mansuy (2000).
Recognition of alpha-amino acids bearing various C=NOH functions by nitric oxide synthase and arginase involves very different structural determinants.
  Biochemistry, 39, 8208-8218.  
10927171 D.W.Reif, D.J.McCarthy, E.Cregan, and J.E.Macdonald (2000).
Discovery and development of neuronal nitric oxide synthase inhibitors.
  Free Radic Biol Med, 28, 1470-1477.  
10671516 H.Shimizu, E.Obayashi, Y.Gomi, H.Arakawa, S.Y.Park, H.Nakamura, S.Adachi, H.Shoun, and Y.Shiro (2000).
Proton delivery in NO reduction by fungal nitric-oxide reductase. Cryogenic crystallography, spectroscopy, and kinetics of ferric-NO complexes of wild-type and mutant enzymes.
  J Biol Chem, 275, 4816-4826.
PDB codes: 1cl6 1cmj 1cmn
10799481 J.M.Perry, Y.Zhao, and M.A.Marletta (2000).
Cu2+ and Zn2+ inhibit nitric-oxide synthase through an interaction with the reductase domain.
  J Biol Chem, 275, 14070-14076.  
10677491 K.McMillan, M.Adler, D.S.Auld, J.J.Baldwin, E.Blasko, L.J.Browne, D.Chelsky, D.Davey, R.E.Dolle, K.A.Eagen, S.Erickson, R.I.Feldman, C.B.Glaser, C.Mallari, M.M.Morrissey, M.H.Ohlmeyer, G.Pan, J.F.Parkinson, G.B.Phillips, M.A.Polokoff, N.H.Sigal, R.Vergona, M.Whitlow, T.A.Young, and J.J.Devlin (2000).
Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry.
  Proc Natl Acad Sci U S A, 97, 1506-1511.
PDB code: 1dd7
10652305 M.Couture, D.J.Stuehr, and D.L.Rousseau (2000).
The ferrous dioxygen complex of the oxygenase domain of neuronal nitric-oxide synthase.
  J Biol Chem, 275, 3201-3205.  
10691780 P.Lane, and S.S.Gross (2000).
The autoinhibitory control element and calmodulin conspire to provide physiological modulation of endothelial and neuronal nitric oxide synthase activity.
  Acta Physiol Scand, 168, 53-63.  
10924132 V.Berka, and A.L.Tsai (2000).
Characterization of interactions among the heme center, tetrahydrobiopterin, and L-arginine binding sites of ferric eNOS using imidazole, cyanide, and nitric oxide as probes.
  Biochemistry, 39, 9373-9383.  
10608822 A.Leber, B.Hemmens, B.Klösch, W.Goessler, G.Raber, B.Mayer, and K.Schmidt (1999).
Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris.
  J Biol Chem, 274, 37658-37664.  
10625434 A.R.Hurshman, C.Krebs, D.E.Edmondson, B.H.Huynh, and M.A.Marletta (1999).
Formation of a pterin radical in the reaction of the heme domain of inducible nitric oxide synthase with oxygen.
  Biochemistry, 38, 15689-15696.  
10464242 B.R.Babu, C.Frey, and O.W.Griffith (1999).
L-arginine binding to nitric-oxide synthase. The role of H-bonds to the nonreactive guanidinium nitrogens.
  J Biol Chem, 274, 25218-25226.  
10562539 B.R.Crane, R.J.Rosenfeld, A.S.Arvai, D.K.Ghosh, S.Ghosh, J.A.Tainer, D.J.Stuehr, and E.D.Getzoff (1999).
N-terminal domain swapping and metal ion binding in nitric oxide synthase dimerization.
  EMBO J, 18, 6271-6281.
PDB codes: 1df1 1qom
10562538 D.K.Ghosh, B.R.Crane, S.Ghosh, D.Wolan, R.Gachhui, C.Crooks, A.Presta, J.A.Tainer, E.D.Getzoff, and D.J.Stuehr (1999).
Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook and pterin-binding segment in dimerization and tetrahydrobiopterin interaction.
  EMBO J, 18, 6260-6270.
PDB codes: 1dwv 1dww 1dwx
10409685 H.Li, C.S.Raman, C.B.Glaser, E.Blasko, T.A.Young, J.F.Parkinson, M.Whitlow, and T.L.Poulos (1999).
Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase.
  J Biol Chem, 274, 21276-21284.
PDB codes: 1nsi 2nsi
10419469 I.Rodríguez-Crespo, C.R.Nishida, G.M.Knudsen, and P.R.de Montellano (1999).
Mutation of the five conserved histidines in the endothelial nitric-oxide synthase hemoprotein domain. No evidence for a non-heme metal requirement for catalysis.
  J Biol Chem, 274, 21617-21624.  
10480877 J.Vásquez-Vivar, N.Hogg, P.Martásek, H.Karoui, K.A.Pritchard, and B.Kalyanaraman (1999).
Tetrahydrobiopterin-dependent inhibition of superoxide generation from neuronal nitric oxide synthase.
  J Biol Chem, 274, 26736-26742.  
10625450 M.Sono, A.P.Ledbetter, K.McMillan, L.J.Roman, T.M.Shea, B.S.Masters, and J.H.Dawson (1999).
Essential thiol requirement to restore pterin- or substrate-binding capability and to regenerate native enzyme-type high-spin heme spectra in the Escherichia coli-expressed tetrahydrobiopterin-free oxygenase domain of neuronal nitric oxide synthase.
  Biochemistry, 38, 15853-15862.  
10480900 S.Adak, C.Crooks, Q.Wang, B.R.Crane, J.A.Tainer, E.D.Getzoff, and D.J.Stuehr (1999).
Tryptophan 409 controls the activity of neuronal nitric-oxide synthase by regulating nitric oxide feedback inhibition.
  J Biol Chem, 274, 26907-26911.  
10480907 T.Shimanuki, H.Sato, S.Daff, I.Sagami, and T.Shimizu (1999).
Crucial role of Lys(423) in the electron transfer of neuronal nitric-oxide synthase.
  J Biol Chem, 274, 26956-26961.  
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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