4ia0: Difference between revisions
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==Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors== | ==Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors== | ||
<StructureSection load='4ia0' size='340' side='right' caption='[[4ia0]], [[Resolution|resolution]] 2.17Å' scene=''> | <StructureSection load='4ia0' size='340' side='right'caption='[[4ia0]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ia0]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4ia0]] 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=4IA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IA0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5BB:5-BROMO-2-{2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-6-OCTYLPYRIMIDIN-4(3H)-ONE'>5BB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.17Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5BB:5-BROMO-2-{2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-6-OCTYLPYRIMIDIN-4(3H)-ONE'>5BB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4ia0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ia0 OCA], [https://pdbe.org/4ia0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ia0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ia0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ia0 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 19: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4ia0" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Phosphodiesterase|Phosphodiesterase]] | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Chen | [[Category: Chen T]] | ||
[[Category: Ren | [[Category: Ren J]] | ||
[[Category: Xu | [[Category: Xu Y]] | ||
Latest revision as of 09:35, 17 October 2024
Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitorsCrystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors
Structural highlights
FunctionPDE5A_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. Publication Abstract from PubMedThe substituents both at the 6-position of the 5-bromopyrimidinone ring and at the 5'-position of the phenyl ring of 5-bromopyrimidin-4(3H)-ones were explored. 5-Bromo-6-isopropyl-2-(2-propoxy-phenyl)pyrimidin-4(3H)-one was identified as a new scaffold for potent PDE5 inhibitors. The crystal structures of PDE5/2e and PDE5/10a complexes provided a structural basis for the inhibition of 5-bromopyrimidinones to PDE5. In addition, it was also found that there is a great tolerance for the substitution at the 5'-position of the phenyl ring of 5-bormopyrimidinones and the resulted compound 13a has the highest inhibition activity to PDE5 (IC50, 1.7 nM). Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5.,Gong X, Wang G, Ren J, Liu Z, Wang Z, Chen T, Yang X, Jiang X, Shen J, Jiang H, Aisa HA, Xu Y, Li J Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. doi: 10.1016/j.bmcl.2013.06.062. , Epub 2013 Jun 29. PMID:23867165[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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