2bhj

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[[Image:2bhj.gif|left|200px]]
 
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{{Structure
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==murine iNO synthase with coumarin inhibitor==
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|PDB= 2bhj |SIZE=350|CAPTION= <scene name='initialview01'>2bhj</scene>, resolution 3.2&Aring;
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<StructureSection load='2bhj' size='340' side='right'caption='[[2bhj]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Hbl+Binding+Site+For+Chain+A'>AC1</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=FC1:THIOCOUMARIN'>FC1</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>
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<table><tr><td colspan='2'>[[2bhj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BHJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BHJ FirstGlance]. <br>
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|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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FC1:THIOCOUMARIN'>FC1</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bhj OCA], [https://pdbe.org/2bhj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bhj RCSB], [https://www.ebi.ac.uk/pdbsum/2bhj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bhj ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bhj OCA], [http://www.ebi.ac.uk/pdbsum/2bhj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bhj RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bh/2bhj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bhj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.
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'''MURINE INO SYNTHASE WITH COUMARIN INHIBITOR'''
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Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase.,Jackson SA, Sahni S, Lee L, Luo Y, Nieduzak TR, Liang G, Chiang Y, Collar N, Fink D, He W, Laoui A, Merrill J, Boffey R, Crackett P, Rees B, Wong M, Guilloteau JP, Mathieu M, Rebello SS Bioorg Med Chem. 2005 Apr 15;13(8):2723-39. PMID:15781384<ref>PMID:15781384</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2bhj" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.
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*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2BHJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BHJ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Large Structures]]
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Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase., Jackson SA, Sahni S, Lee L, Luo Y, Nieduzak TR, Liang G, Chiang Y, Collar N, Fink D, He W, Laoui A, Merrill J, Boffey R, Crackett P, Rees B, Wong M, Guilloteau JP, Mathieu M, Rebello SS, Bioorg Med Chem. 2005 Apr 15;13(8):2723-39. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15781384 15781384]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Nitric-oxide synthase]]
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[[Category: Guilloteau JP]]
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[[Category: Single protein]]
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[[Category: Mathieu M]]
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[[Category: Guilloteau, J P.]]
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[[Category: Mathieu, M.]]
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[[Category: calmodulin-binding]]
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[[Category: fad]]
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[[Category: fmn]]
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[[Category: heme]]
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[[Category: ino]]
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[[Category: metal-binding]]
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[[Category: nadp]]
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[[Category: oxidoreductase]]
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[[Category: polymorphism]]
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[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:06:30 2008''
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Current revision

murine iNO synthase with coumarin inhibitor

PDB ID 2bhj

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