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| | <StructureSection load='1so2' size='340' side='right'caption='[[1so2]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1so2' size='340' side='right'caption='[[1so2]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1so2]] is a 4 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=1SO2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1SO2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1so2]] is a 4 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=1SO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SO2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=666:6-(4-{[2-(3-IODOBENZYL)-3-OXOCYCLOHEX-1-EN-1-YL]AMINO}PHENYL)-5-METHYL-4,5-DIHYDROPYRIDAZIN-3(2H)-ONE'>666</scene>, <scene name='pdbligand=HG9:1-DEOXY-1-[(2-HYDROXYETHYL)(NONANOYL)AMINO]HEXITOL'>HG9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1soj|1soj]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=666:6-(4-{[2-(3-IODOBENZYL)-3-OXOCYCLOHEX-1-EN-1-YL]AMINO}PHENYL)-5-METHYL-4,5-DIHYDROPYRIDAZIN-3(2H)-ONE'>666</scene>, <scene name='pdbligand=HG9:1-DEOXY-1-[(2-HYDROXYETHYL)(NONANOYL)AMINO]HEXITOL'>HG9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE3B ([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=1so2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1so2 OCA], [https://pdbe.org/1so2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1so2 RCSB], [https://www.ebi.ac.uk/pdbsum/1so2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1so2 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-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1so2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1so2 OCA], [http://pdbe.org/1so2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1so2 RCSB], [http://www.ebi.ac.uk/pdbsum/1so2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1so2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDE3B_HUMAN PDE3B_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:21393242</ref> <ref>PMID:15147193</ref> | + | [https://www.uniprot.org/uniprot/PDE3B_HUMAN PDE3B_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:21393242</ref> <ref>PMID:15147193</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Becker, J W]] | + | [[Category: Becker JW]] |
| - | [[Category: Chung, C]] | + | [[Category: Chung C]] |
| - | [[Category: Edmondson, S D]] | + | [[Category: Edmondson SD]] |
| - | [[Category: Mastracchio, A]] | + | [[Category: Mastracchio A]] |
| - | [[Category: Parmee, E R]] | + | [[Category: Parmee ER]] |
| - | [[Category: Patel, S B]] | + | [[Category: Patel SB]] |
| - | [[Category: Ploeg, L H.Van Der]]
| + | [[Category: Scapin G]] |
| - | [[Category: Scapin, G]] | + | [[Category: Singh SB]] |
| - | [[Category: Singh, S B]] | + | [[Category: Tota MR]] |
| - | [[Category: Tota, M R]] | + | [[Category: Van Der Ploeg LH]] |
| - | [[Category: Varnerin, J P]] | + | [[Category: Varnerin JP]] |
| - | [[Category: Hydrolase]] | + | |
| - | [[Category: Pde3b phosphodiesterase]]
| + | |
| Structural highlights
Function
PDE3B_HUMAN Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Phosphodiesterases (PDEs) are enzymes that modulate cyclic nucleotide signaling and as such are clinical targets for a range of disorders including congestive heart failure, erectile dysfunction, and inflammation. The PDE3 family comprises two highly homologous subtypes expressed in different tissues, and inhibitors of this family have been shown to increase lipolysis in adipocytes. A specific PDE3B (the lipocyte-localized subtype) inhibitor would be a very useful tool to evaluate the effects of PDE3 inhibition on lipolysis and metabolic rate and might become a novel tool for treatment of obesity. We report here the three-dimensional structures of the catalytic domain of human PDE3B in complex with a generic PDE inhibitor and a novel PDE3 selective inhibitor. These structures explain the dual cAMP/cGMP binding capabilities of PDE3, provide the molecular basis for inhibitor specificity, and can supply a valid platform for the design of improved compounds.
Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and inhibitor specificity.,Scapin G, Patel SB, Chung C, Varnerin JP, Edmondson SD, Mastracchio A, Parmee ER, Singh SB, Becker JW, Van der Ploeg LH, Tota MR Biochemistry. 2004 May 25;43(20):6091-100. PMID:15147193[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wilson LS, Baillie GS, Pritchard LM, Umana B, Terrin A, Zaccolo M, Houslay MD, Maurice DH. A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. J Biol Chem. 2011 May 6;286(18):16285-96. doi: 10.1074/jbc.M110.217026. Epub 2011, Mar 10. PMID:21393242 doi:10.1074/jbc.M110.217026
- ↑ Scapin G, Patel SB, Chung C, Varnerin JP, Edmondson SD, Mastracchio A, Parmee ER, Singh SB, Becker JW, Van der Ploeg LH, Tota MR. Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and inhibitor specificity. Biochemistry. 2004 May 25;43(20):6091-100. PMID:15147193 doi:10.1021/bi049868i
- ↑ Scapin G, Patel SB, Chung C, Varnerin JP, Edmondson SD, Mastracchio A, Parmee ER, Singh SB, Becker JW, Van der Ploeg LH, Tota MR. Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and inhibitor specificity. Biochemistry. 2004 May 25;43(20):6091-100. PMID:15147193 doi:10.1021/bi049868i
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