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| | <StructureSection load='4md6' size='340' side='right'caption='[[4md6]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4md6' size='340' side='right'caption='[[4md6]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4md6]] 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=4MD6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MD6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4md6]] 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=4MD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MD6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=24E:3-(4-HYDROXYBENZYL)-1-(THIOPHEN-2-YL)CHROMENO[2,3-C]PYRROL-9(2H)-ONE'>24E</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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=24E:3-(4-HYDROXYBENZYL)-1-(THIOPHEN-2-YL)CHROMENO[2,3-C]PYRROL-9(2H)-ONE'>24E</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE5A, PDE5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4md6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md6 OCA], [https://pdbe.org/4md6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4md6 RCSB], [https://www.ebi.ac.uk/pdbsum/4md6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4md6 ProSAT]</span></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=4md6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md6 OCA], [http://pdbe.org/4md6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4md6 RCSB], [http://www.ebi.ac.uk/pdbsum/4md6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4md6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [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 == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phosphodiesterase|Phosphodiesterase]] | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3',5'-cyclic-GMP phosphodiesterase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cui, W]] | + | [[Category: Cui W]] |
| - | [[Category: Huang, M]] | + | [[Category: Huang M]] |
| - | [[Category: Luo, H]] | + | [[Category: Luo H]] |
| - | [[Category: Shao, Y]] | + | [[Category: Shao Y]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Pde5 inhibitor]]
| + | |
| - | [[Category: Phosphodiesterase]]
| + | |
| - | [[Category: Protein-inhibitor complex]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of PDE5 inhibitors continues for their potential new applications. Reported here is discovery of a series of new PDE5 inhibitors by structure-based design, molecular docking, chemical synthesis, and enzymatic characterization. The best compound, 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an IC(5)(0) of 17 nM against the PDE5 catalytic domain and good selectivity over other PDE families. The crystal structure of the PDE5 catalytic domain in complex with 57 was determined at 2A resolution and showed that 57 occupies the same pocket as other PDE5 inhibitors, but has a different binding pattern in detail. On the basis of the binding pattern of 57, a novel scaffold can be proposed as a candidate of PDE inhibitors.
Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure.,Shang NN, Shao YX, Cai YH, Guan M, Huang M, Cui W, He L, Yu YJ, Huang L, Li Z, Bu XZ, Ke H, Luo HB Biochem Pharmacol. 2014 May 1;89(1):86-98. doi: 10.1016/j.bcp.2014.02.013. Epub, 2014 Feb 22. PMID:24565909[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shang NN, Shao YX, Cai YH, Guan M, Huang M, Cui W, He L, Yu YJ, Huang L, Li Z, Bu XZ, Ke H, Luo HB. Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure. Biochem Pharmacol. 2014 May 1;89(1):86-98. doi: 10.1016/j.bcp.2014.02.013. Epub, 2014 Feb 22. PMID:24565909 doi:http://dx.doi.org/10.1016/j.bcp.2014.02.013
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