6l6e
From Proteopedia
(Difference between revisions)
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==Human PDE5 catalytic core in complex with avanafil== | ==Human PDE5 catalytic core in complex with avanafil== | ||
| - | <StructureSection load='6l6e' size='340' side='right'caption='[[6l6e]]' scene=''> | + | <StructureSection load='6l6e' size='340' side='right'caption='[[6l6e]], [[Resolution|resolution]] 1.92Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L6E OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6l6e]] is a 1 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=6L6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L6E FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E6L:4-[(3-chloranyl-4-methoxy-phenyl)methylamino]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimid+ine-5-carboxamide'>E6L</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6l6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l6e OCA], [https://pdbe.org/6l6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l6e RCSB], [https://www.ebi.ac.uk/pdbsum/6l6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l6e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Phosphodiesterase 5A1 (PDE5) is a key target for treating cardiovascular diseases and erectile dysfunction. Here, we report the crystal structure of PDE5 complexed with the sole second generation drug avanafil. Analysis of protein-drug interactions revealed the structural basis of avanafil's superior isoform selectivity. Moreover, a halogen bonding was observed between avanafil and a backbone carbonyl oxygen of an adjacent alpha-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting alpha-helix backbone in structure-based drug design. | ||
| + | |||
| + | Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting alpha-Helix Backbone Oxygen by Halogen Bonding.,Hsieh CM, Chen CY, Chern JW, Chan NL J Med Chem. 2020 Aug 13;63(15):8485-8494. doi: 10.1021/acs.jmedchem.0c00853. Epub, 2020 Jul 27. PMID:32663396<ref>PMID:32663396</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6l6e" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chan NL]] | [[Category: Chan NL]] | ||
[[Category: Hsieh CM]] | [[Category: Hsieh CM]] | ||
Current revision
Human PDE5 catalytic core in complex with avanafil
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