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1vaf
From Proteopedia
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|PDB= 1vaf |SIZE=350|CAPTION= <scene name='initialview01'>1vaf</scene>, resolution 2.9Å | |PDB= 1vaf |SIZE=350|CAPTION= <scene name='initialview01'>1vaf</scene>, resolution 2.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ARR:N-(4-{2-[(3-CHLOROBENZYL)AMINO]ETHYL}PHENYL)THIOPHENE-2-CARBOXIMIDAMIDE'>ARR</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= NOS2, INOSL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | |GENE= NOS2, INOSL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1qw4|1QW4]], [[1qw5|1QW5]], [[1qw6|1QW6]], [[1qwc|1QWC]], [[1vag|1VAG]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vaf OCA], [http://www.ebi.ac.uk/pdbsum/1vaf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1vaf RCSB]</span> | ||
}} | }} | ||
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[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
[[Category: Vasan, R.]] | [[Category: Vasan, R.]] | ||
| - | [[Category: ARR]] | ||
| - | [[Category: H4B]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: ZN]] | ||
[[Category: murine inosoxy inhibitor complex]] | [[Category: murine inosoxy inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:21:42 2008'' |
Revision as of 21:21, 30 March 2008
| |||||||
| , resolution 2.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | NOS2, INOSL (Mus musculus) | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Related: | 1QW4, 1QW5, 1QW6, 1QWC, 1VAG
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Inducible 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
1VAF is a Single protein structure of sequence from Mus musculus. 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
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