1zvi

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(New page: 200px<br /><applet load="1zvi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zvi, resolution 2.0&Aring;" /> '''Rat Neuronal Nitric O...)
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[[Image:1zvi.gif|left|200px]]<br /><applet load="1zvi" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zvi, resolution 2.0&Aring;" />
 
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'''Rat Neuronal Nitric Oxide Synthase Oxygenase Domain'''<br />
 
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==Overview==
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==Rat Neuronal Nitric Oxide Synthase Oxygenase Domain==
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Nitric oxide synthesized from l-arginine by nitric oxide synthase isoforms, (NOS-I-III) is physiologically important but also can be deleterious when, overproduced. Selective NOS inhibitors are of clinical interest, given, their differing pathophysiological roles. Here we describe our approach to, target the unique NOS (6R,1'R,2'S)-5,6,7,8-tetrahydrobiopterin (H(4)Bip), binding site. By a combination of ligand- and structure-based design, the, structure-activity relationship (SAR) for a focused set of 41 pteridine, analogues on four scaffolds was developed, revealing selective NOS-I, inhibitors. The X-ray crystal structure of rat NOS-I dimeric-oxygenase, domain with H(4)Bip and l-arginine was determined and used for human, isoform homology modeling. All available NOS structural information was, subjected to comparative analysis of favorable protein-ligand interactions, using the GRID/concensus principal component analysis (CPCA) approach to, identify the isoform-specific interaction site. Our interpretation, based, on protein structures, is in good agreement with the ligand SAR and thus, permits the rational design of next-generation inhibitors targeting the, H(4)Bip binding site with enhanced isoform selectivity for therapeutics in, pathology with NO overproduction.
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<StructureSection load='1zvi' size='340' side='right'caption='[[1zvi]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zvi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZVI FirstGlance]. <br>
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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]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
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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=1zvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvi OCA], [https://pdbe.org/1zvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zvi RCSB], [https://www.ebi.ac.uk/pdbsum/1zvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zvi ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
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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/zv/1zvi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1zvi ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1ZVI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN, HEM and H4B as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZVI OCA].
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*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural analysis of isoform-specific inhibitors targeting the tetrahydrobiopterin binding site of human nitric oxide synthases., Matter H, Kumar HS, Fedorov R, Frey A, Kotsonis P, Hartmann E, Frohlich LG, Reif A, Pfleiderer W, Scheurer P, Ghosh DK, Schlichting I, Schmidt HH, J Med Chem. 2005 Jul 28;48(15):4783-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16033258 16033258]
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[[Category: Large Structures]]
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[[Category: Nitric-oxide synthase]]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Fedorov R]]
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[[Category: Fedorov, R.]]
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[[Category: Frey A]]
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[[Category: Frey, A.]]
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[[Category: Frohlich LG]]
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[[Category: Frohlich, L.G.]]
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[[Category: Ghosh DK]]
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[[Category: Ghosh, D.K.]]
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[[Category: Hartmann E]]
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[[Category: Hartmann, E.]]
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[[Category: Kotsonis P]]
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[[Category: Kotsonis, P.]]
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[[Category: Kumar HS]]
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[[Category: Kumar, H.S.]]
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[[Category: Matter H]]
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[[Category: Matter, H.]]
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[[Category: Pfleiderer W]]
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[[Category: Pfleiderer, W.]]
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[[Category: Reif A]]
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[[Category: Reif, A.]]
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[[Category: Scheurer P]]
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[[Category: Scheurer, P.]]
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[[Category: Schlichting I]]
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[[Category: Schlichting, I.]]
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[[Category: Schmidt HH]]
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[[Category: Schmidt, H.H.]]
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[[Category: H4B]]
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[[Category: HEM]]
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[[Category: ZN]]
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[[Category: rat nnosoxy]]
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[[Category: targeting tetrahydrobiopterin binding site]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:41:18 2007''
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Current revision

Rat Neuronal Nitric Oxide Synthase Oxygenase Domain

PDB ID 1zvi

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