View source for 3jwq


==Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafil==
<StructureSection load='3jwq' size='340' side='right'caption='[[3jwq]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3jwq]] 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=3JWQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JWQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VIA:5-{2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-1-METHYL-3-PROPYL-1H,6H,7H-PYRAZOLO[4,3-D]PYRIMIDIN-7-ONE'>VIA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3jwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwq OCA], [https://pdbe.org/3jwq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jwq RCSB], [https://www.ebi.ac.uk/pdbsum/3jwq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jwq ProSAT]</span></td></tr>
</table>
== Disease ==
[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.
== Function ==
[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] 
== 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/jw/3jwq_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=3jwq ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3jwq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calcium/calmodulin dependent protein kinase 3D structures|Calcium/calmodulin dependent protein kinase 3D structures]]
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Artemyev NO]]
[[Category: Barren B]]
[[Category: Boyd KK]]
[[Category: Gakhar L]]
[[Category: Muradov H]]
[[Category: Ramaswamy S]]