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1vag
From Proteopedia
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| - | [[Image:1vag.gif|left|200px]] | + | [[Image:1vag.gif|left|200px]] |
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| - | '''Neuronal nitric oxide synthase oxygenase domain complexed with the inhibitor AR-R17477''' | + | {{Structure |
| + | |PDB= 1vag |SIZE=350|CAPTION= <scene name='initialview01'>1vag</scene>, resolution 2.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene> and <scene name='pdbligand=ARR:N-(4-{2-[(3-CHLOROBENZYL)AMINO]ETHYL}PHENYL)THIOPHENE-2-CARBOXIMIDAMIDE'>ARR</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] | ||
| + | |GENE= NOS1, BNOS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | }} | ||
| + | |||
| + | '''Neuronal nitric oxide synthase oxygenase domain complexed with the inhibitor AR-R17477''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1VAG is a [ | + | 1VAG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VAG OCA]. |
==Reference== | ==Reference== | ||
| - | Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design., Fedorov R, Vasan R, Ghosh DK, Schlichting I, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5892-7. Epub 2004 Apr 7. PMID:[http:// | + | Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design., Fedorov R, Vasan R, Ghosh DK, Schlichting I, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5892-7. Epub 2004 Apr 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15071192 15071192] |
[[Category: Nitric-oxide synthase]] | [[Category: Nitric-oxide synthase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
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[[Category: rat nnosoxy complex with ar-r17477]] | [[Category: rat nnosoxy complex with ar-r17477]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:42:54 2008'' |
Revision as of 12:42, 20 March 2008
| |||||||
| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | NOS1, BNOS (Rattus norvegicus) | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Neuronal nitric oxide synthase oxygenase domain complexed with the inhibitor AR-R17477
Overview
The high level of amino acid conservation and structural similarity of the substrate-binding sites of the oxygenase domains of the nitric oxide synthase (NOS) isoforms (eNOSoxy, iNOSoxy, nNOSoxy) make the interpretation of the structural basis of inhibitor isoform specificity a challenge, and provide few clues for the design of new selective compounds. Crystal structures of iNOSoxy and nNOSoxy complexed with the neuronal NOS-specific inhibitor AR-R17447 suggest that specificity is provided by the interaction of the chlorophenyl group with an isoform-unique substrate access channel residue (L337 in rat neuronal NOS, N115 in mouse inducible NOS). This is confirmed by biochemical analysis of site-directed mutants. Inhibitors combining guanidinium-like structural motifs with long chains specifically targeting this residue are good candidates for rational isoform-specific drug design. Based on this finding, modifications of AR-R17447 to improve the specificity for the human isoforms are suggested.
About this Structure
1VAG is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design., Fedorov R, Vasan R, Ghosh DK, Schlichting I, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5892-7. Epub 2004 Apr 7. PMID:15071192
Page seeded by OCA on Thu Mar 20 14:42:54 2008
