4g2w: Difference between revisions
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== | ==Crystal structure of PDE5A in complex with its inhibitor== | ||
[[http://www.uniprot.org/uniprot/PDE5A_HUMAN PDE5A_HUMAN | <StructureSection load='4g2w' size='340' side='right'caption='[[4g2w]], [[Resolution|resolution]] 2.28Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4g2w]] 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=4G2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G2W 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]] 2.28Å</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=NI0:5,6-DIETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE'>NI0</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=4g2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g2w OCA], [https://pdbe.org/4g2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g2w RCSB], [https://www.ebi.ac.uk/pdbsum/4g2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g2w ProSAT]</span></td></tr> | |||
</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 == | |||
Cyclic nucleotide phosphodiesterase type 5 (PDE5) is a prime drug target for treating the diseases associated with a lower level of the cyclic guanosine monophosphate (cGMP), which is a specific substrate for PDE5 hydrolysis. Here we report a series of novel PDE5 inhibitors with the new scaffold of the monocyclic pyrimidin-4(3H)-one ring developed using the structure-based discovery strategy. In total, 37 derivatives of the pyrimidin-4(3H)-ones, were designed, synthesized, and evaluated for their inhibitory activities to PDE5, resulting in 25 compounds with IC50 ranging from 1 to 100 nM and 11 compounds with IC50 ranging from 1 to 10 nM. Compound 5, 5,6-diethyl-2-[2-n-propoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]pyrimid-4(3H) -one, the most potent compound, has an excellent IC50 (1.6 nM) in vitro and a good efficacy in a rat model of erection. It thus provides a potential candidate for the further development into a new drug targeting PDE5. | |||
Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5.,Wang G, Liu Z, Chen T, Wang Z, Yang H, Zheng M, Ren J, Tian G, Yang X, Li L, Li J, Suo J, Zhang R, Jiang X, Terrett NK, Shen J, Xu Y, Jiang H J Med Chem. 2012 Dec 13;55(23):10540-50. doi: 10.1021/jm301159y. Epub 2012 Nov, 19. PMID:23137303<ref>PMID:23137303</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
< | </div> | ||
[[ | <div class="pdbe-citations 4g2w" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Chen TT]] | ||
[[Category: | [[Category: Ren J]] | ||
[[Category: | [[Category: Xu YC]] | ||
Latest revision as of 13:55, 8 November 2023
Crystal structure of PDE5A in complex with its inhibitor
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