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{{Seed}}
[[Image:3l6j.jpg|left|200px]]


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==Structure of cinaciguat (bay 58-2667) bound to nostoc H-NOX domain==
The line below this paragraph, containing "STRUCTURE_3l6j", creates the "Structure Box" on the page.
<StructureSection load='3l6j' size='340' side='right'caption='[[3l6j]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3l6j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nostoc_sp._PCC_7120_=_FACHB-418 Nostoc sp. PCC 7120 = FACHB-418]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L6J FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#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=Z90:4-({(4-CARBOXYBUTYL)[2-(2-{[4-(2-PHENYLETHYL)BENZYL]OXY}PHENYL)ETHYL]AMINO}METHYL)BENZOIC+ACID'>Z90</scene></td></tr>
{{STRUCTURE_3l6j|  PDB=3l6j  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l6j OCA], [https://pdbe.org/3l6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l6j RCSB], [https://www.ebi.ac.uk/pdbsum/3l6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l6j ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8YUQ7_NOSS1 Q8YUQ7_NOSS1]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l6/3l6j_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3l6j ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Heme is a vital molecule for all life forms with heme being capable of assisting in catalysis, binding ligands, and undergoing redox changes. Heme-related dysfunction can lead to cardiovascular diseases with the oxidation of the heme of soluble guanylyl cyclase (sGC) critically implicated in some of these cardiovascular diseases. sGC, the main nitric oxide (NO) receptor, stimulates second messenger cGMP production, whereas reactive oxygen species are known to scavenge NO and oxidize/inactivate the heme leading to sGC degradation. This vulnerability of NO-heme signaling to oxidative stress led to the discovery of an NO-independent activator of sGC, cinaciguat (BAY 58-2667), which is a candidate drug in clinical trials to treat acute decompensated heart failure. Here, we present crystallographic and mutagenesis data that reveal the mode of action of BAY 58-2667. The 2.3-A resolution structure of BAY 58-2667 bound to a heme NO and oxygen binding domain (H-NOX) from Nostoc homologous to that of sGC reveals that the trifurcated BAY 58-2667 molecule has displaced the heme and acts as a heme mimetic. Carboxylate groups of BAY 58-2667 make interactions similar to the heme-propionate groups, whereas its hydrophobic phenyl ring linker folds up within the heme cavity in a planar-like fashion. BAY 58-2667 binding causes a rotation of the alphaF helix away from the heme pocket, as this helix is normally held in place via the inhibitory His(105)-heme covalent bond. The structure provides insights into how BAY 58-2667 binds and activates sGC to rescue heme-NO dysfunction in cardiovascular diseases.


===Structure of cinaciguat (bay 58-2667) bound to nostoc H-NOX domain===
Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase.,Martin F, Baskaran P, Ma X, Dunten PW, Schaefer M, Stasch JP, Beuve A, van den Akker F J Biol Chem. 2010 Jul 16;285(29):22651-7. Epub 2010 May 12. PMID:20463019<ref>PMID:20463019</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==About this Structure==
</div>
3L6J is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Nostoc_sp. Nostoc sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L6J OCA].
<div class="pdbe-citations 3l6j" style="background-color:#fffaf0;"></div>
[[Category: Nostoc sp.]]
== References ==
[[Category: Akker, F van den.]]
<references/>
[[Category: Martin, F.]]
__TOC__
[[Category: Bay58-2667]]
</StructureSection>
[[Category: Guanylyl cyclase]]
[[Category: Large Structures]]
[[Category: Signaling protein]]
[[Category: Nostoc sp. PCC 7120 = FACHB-418]]
 
[[Category: Martin F]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 12 11:17:38 2010''
[[Category: Van den Akker F]]

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