5zz2: Difference between revisions

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-'''Unreleased structure'''
-The entry 5zz2 is ON HOLD  until Paper Publication
+==Crystal structure of PDE5 in complex with inhibitor LW1634==
+<StructureSection load='5zz2' size='340' side='right' caption='[[5zz2]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5zz2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZZ2 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9M0:3-[(2H-1,3-benzodioxol-5-yl)methyl]-8-fluoro-1-(1,3-thiazol-2-yl)[1]benzopyrano[2,3-c]pyrrol-9(2H)-one'>9M0</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='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=5zz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zz2 OCA], [http://pdbe.org/5zz2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zz2 RCSB], [http://www.ebi.ac.uk/pdbsum/5zz2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zz2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://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 ==
+To further explore the structure-activity relationship around the chromeno[2,3- c]pyrrol-9(2 H)-one scaffold, 19 derivatives as inhibitors against PDE5 were discovered. The most potent inhibitor 3 has an IC50 of 0.32 nM with remarkable selectivity and druglike profile. Oral administration of 3 (1.25 mg/kg) caused comparable therapeutic effects to sildenafil (10.0 mg/kg) against pulmonary arterial hypertension. Further, different binding patterns from sildenafil were revealed in cocrystal structures, which provide structural templates for discovery of highly potent PDE5 inhibitors.
-Authors:
+Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension.,Wu D, Huang Y, Chen Y, Huang YY, Geng H, Zhang T, Zhang C, Li Z, Guo L, Chen J, Luo HB J Med Chem. 2018 Sep 7. doi: 10.1021/acs.jmedchem.8b01209. PMID:30148362<ref>PMID:30148362</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5zz2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: 3',5'-cyclic-GMP phosphodiesterase]]
+[[Category: Huang, Y D]]
+[[Category: Huang, Y Y]]
+[[Category: Luo, H B]]
+[[Category: Wu, D]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Pde5 inhibitor lw1634]]