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1p6m

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(New page: 200px<br /><applet load="1p6m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p6m, resolution 2.27&Aring;" /> '''Bovine endothelial N...)
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[[Image:1p6m.jpg|left|200px]]<br /><applet load="1p6m" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1p6m, resolution 2.27&Aring;" />
 
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'''Bovine endothelial NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound'''<br />
 
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==Overview==
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==Bovine endothelial NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound==
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Three nitric oxide synthase (NOS) isoforms, eNOS, nNOS and iNOS, generate, nitric oxide (NO) crucial to the cardiovascular, nervous and host defense, systems, respectively. Development of isoform-selective NOS inhibitors is, of considerable therapeutic importance. Crystal structures of, nNOS-selective dipeptide inhibitors in complex with both nNOS and eNOS, were solved and the inhibitors were found to adopt a curled conformation, in nNOS but an extended conformation in eNOS. We hypothesized that a, single-residue difference in the active site, Asp597 (nNOS) versus Asn368, (eNOS), is responsible for the favored binding in nNOS. In the D597N nNOS, mutant crystal structure, a bound inhibitor switches to the extended, conformation and its inhibition of nNOS decreases &gt;200-fold. Therefore, a, single-residue difference is responsible for more than two orders of, magnitude selectivity in inhibition of nNOS over eNOS by, L-N(omega)-nitroarginine-containing dipeptide inhibitors.
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<StructureSection load='1p6m' size='340' side='right'caption='[[1p6m]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1p6m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P6M 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]] 2.27&#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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=DP3:N-{(4S)-4-AMINO-5-[(2-AMINOETHYL)AMINO]PENTYL}-N-NITROGUANIDINE'>DP3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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></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=1p6m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p6m OCA], [https://pdbe.org/1p6m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p6m RCSB], [https://www.ebi.ac.uk/pdbsum/1p6m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p6m ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
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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/p6/1p6m_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=1p6m 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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1P6M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CAC, ACT, ZN, HEM, H4B, DP3 and GOL 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=1P6M 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 basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase., Flinspach ML, Li H, Jamal J, Yang W, Huang H, Hah JM, Gomez-Vidal JA, Litzinger EA, Silverman RB, Poulos TL, Nat Struct Mol Biol. 2004 Jan;11(1):54-9. Epub 2003 Dec 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14718923 14718923]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Nitric-oxide synthase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Flinspach ML]]
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[[Category: Flinspach, M.L.]]
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[[Category: Gomez-Vidal JA]]
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[[Category: Gomez-Vidal, J.A.]]
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[[Category: Hah J-M]]
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[[Category: Hah, J.M.]]
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[[Category: Huang H]]
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[[Category: Huang, H.]]
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[[Category: Jamal J]]
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[[Category: Jamal, J.]]
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[[Category: Li H]]
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[[Category: Li, H.]]
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[[Category: Litzinger EA]]
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[[Category: Litzinger, E.A.]]
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[[Category: Poulos TL]]
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[[Category: Poulos, T.L.]]
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[[Category: Silverman RB]]
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[[Category: Silverman, R.B.]]
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[[Category: Yang W]]
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[[Category: Yang, W.]]
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[[Category: ACT]]
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[[Category: CAC]]
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[[Category: DP3]]
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[[Category: GOL]]
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[[Category: H4B]]
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[[Category: HEM]]
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[[Category: ZN]]
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[[Category: heme-enzyme]]
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[[Category: nitric oxide synthase]]
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[[Category: oxidoreductase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:31:23 2007''
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Current revision

Bovine endothelial NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound

PDB ID 1p6m

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