3jwq: Difference between revisions
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==Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafil== | ==Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafil== | ||
<StructureSection load='3jwq' size='340' side='right' caption='[[3jwq]], [[Resolution|resolution]] 2.87Å' scene=''> | <StructureSection load='3jwq' size='340' side='right' caption='[[3jwq]], [[Resolution|resolution]] 2.87Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE5A, PDE5, PDE6C, PDEA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE5A, PDE5, PDE6C, PDEA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-GMP_phosphodiesterase 3',5'-cyclic-GMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.35 3.1.4.35] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-GMP_phosphodiesterase 3',5'-cyclic-GMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.35 3.1.4.35] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwq OCA], [http://pdbe.org/3jwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jwq RCSB], [http://www.ebi.ac.uk/pdbsum/3jwq PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwq OCA], [http://pdbe.org/3jwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jwq RCSB], [http://www.ebi.ac.uk/pdbsum/3jwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jwq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 3jwq" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3jwq" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 03:46, 16 November 2017
Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafilCrystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafil
Structural highlights
Function[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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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