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3jwr

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{{Seed}}
 
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[[Image:3jwr.jpg|left|200px]]
 
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==Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.==
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The line below this paragraph, containing "STRUCTURE_3jwr", creates the "Structure Box" on the page.
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<StructureSection load='3jwr' size='340' side='right'caption='[[3jwr]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3jwr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JWR FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.994&#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=IBM:3-ISOBUTYL-1-METHYLXANTHINE'>IBM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3jwr| PDB=3jwr | SCENE= }}
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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=3jwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwr OCA], [https://pdbe.org/3jwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jwr RCSB], [https://www.ebi.ac.uk/pdbsum/3jwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jwr ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PDE6C_HUMAN PDE6C_HUMAN] Progressive cone dystrophy;Achromatopsia. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/PDE5A_HUMAN PDE5A_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.[https://www.uniprot.org/uniprot/PDE6C_HUMAN PDE6C_HUMAN]
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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/jw/3jwr_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=3jwr 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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The inhibitory interaction of phosphodiesterase-6 (PDE6) with its gamma-subunit (Pgamma) is pivotal in vertebrate phototransduction. Here, crystal structures of a chimaeric PDE5/PDE6 catalytic domain (PDE5/6cd) complexed with sildenafil or 3-isobutyl-1-methylxanthine and the Pgamma-inhibitory peptide Pgamma(70-87) have been determined at 2.9 and 3.0 A, respectively. These structures show the determinants and the mechanism of the PDE6 inhibition by Pgamma and suggest the conformational change of Pgamma on transducin activation. Two variable H- and M-loops of PDE5/6cd form a distinct interface that contributes to the Pgamma-binding site. This allows the Pgamma C-terminus to fit into the opening of the catalytic pocket, blocking cGMP access to the active site. Our analysis suggests that disruption of the H-M loop interface and Pgamma-binding site is a molecular cause of retinal degeneration in atrd3 mice. Comparison of the two PDE5/6cd structures shows an overlap between the sildenafil and Pgamma(70-87)-binding sites, thereby providing critical insights into the side effects of PDE5 inhibitors on vision.
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===Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.===
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Structural basis of phosphodiesterase 6 inhibition by the C-terminal region of the gamma-subunit.,Barren B, Gakhar L, Muradov H, Boyd KK, Ramaswamy S, Artemyev NO EMBO J. 2009 Nov 18;28(22):3613-22. Epub 2009 Oct 1. PMID:19798052<ref>PMID:19798052</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 3jwr" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19798052}}, adds the Publication Abstract to the page
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19798052 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19798052}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3JWR is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JWR OCA].
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==Reference==
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<ref group="xtra">PMID:19798052</ref><references group="xtra"/>
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[[Category: 3',5'-cyclic-GMP phosphodiesterase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Artemyev, N O.]]
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[[Category: Large Structures]]
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[[Category: Barren, B.]]
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[[Category: Artemyev NO]]
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[[Category: Boyd, K K.]]
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[[Category: Barren B]]
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[[Category: Gakhar, L.]]
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[[Category: Boyd KK]]
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[[Category: Muradov, H.]]
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[[Category: Gakhar L]]
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[[Category: Ramaswamy, S.]]
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[[Category: Muradov H]]
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[[Category: Cgmp]]
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[[Category: Ramaswamy S]]
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[[Category: Hydrolase]]
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[[Category: Mostly alpha]]
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[[Category: Polymorphism]]
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[[Category: Sensory transduction]]
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[[Category: Vision]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 14 10:16:56 2009''
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Current revision

Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.

PDB ID 3jwr

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