4i9z
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors== | |
| - | + | <StructureSection load='4i9z' size='340' side='right' caption='[[4i9z]], [[Resolution|resolution]] 2.08Å' scene=''> | |
| - | { | + | == Structural highlights == |
| + | <table><tr><td colspan='2'>[[4i9z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I9Z FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5BA:5-BROMO-2-{5-[(4-METHYLPIPERAZIN-1-YL)ACETYL]-2-PROPOXYPHENYL}-6-(PROPAN-2-YL)PYRIMIDIN-4(3H)-ONE'>5BA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ia0|4ia0]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE5, PDE5A ([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='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=4i9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i9z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i9z RCSB], [http://www.ebi.ac.uk/pdbsum/4i9z PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The 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<ref>PMID:23867165</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | + | *[[Phosphodiesterase|Phosphodiesterase]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: 3',5'-cyclic-GMP phosphodiesterase]] | [[Category: 3',5'-cyclic-GMP phosphodiesterase]] | ||
| - | [[Category: Chen, T | + | [[Category: Human]] |
| - | [[Category: Ren, J | + | [[Category: Chen, T]] |
| - | [[Category: Xu, Y | + | [[Category: Ren, J]] |
| + | [[Category: Xu, Y]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 16:51, 21 December 2014
Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors
| |||||||||||
