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| | ==Catalytic Domain of Human Phosphodiesterase 4B in Complex with A Coumarin-Based Inhibitor== | | ==Catalytic Domain of Human Phosphodiesterase 4B in Complex with A Coumarin-Based Inhibitor== |
| - | <StructureSection load='3ly2' size='340' side='right' caption='[[3ly2]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='3ly2' size='340' side='right'caption='[[3ly2]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ly2]] is a 8 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=3LY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LY2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ly2]] is a 8 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=3LY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LY2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Z72:8-(CYCLOPENTYLOXY)-4-[(3,5-DICHLOROPYRIDIN-4-YL)AMINO]-7-METHOXY-2H-CHROMEN-2-ONE'>Z72</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xlx|1xlx]], [[1xlz|1xlz]], [[1xm4|1xm4]], [[1xm6|1xm6]], [[1xmu|1xmu]], [[1xmy|1xmy]]</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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Z72:8-(CYCLOPENTYLOXY)-4-[(3,5-DICHLOROPYRIDIN-4-YL)AMINO]-7-METHOXY-2H-CHROMEN-2-ONE'>Z72</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">DPDE4, PDE4B ([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=3ly2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ly2 OCA], [https://pdbe.org/3ly2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ly2 RCSB], [https://www.ebi.ac.uk/pdbsum/3ly2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ly2 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ly2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ly2 OCA], [http://pdbe.org/3ly2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ly2 RCSB], [http://www.ebi.ac.uk/pdbsum/3ly2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ly2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDE4B_HUMAN PDE4B_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref> | + | [https://www.uniprot.org/uniprot/PDE4B_HUMAN PDE4B_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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-nucleotide phosphodiesterase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Coyle, A R]] | + | [[Category: Coyle AR]] |
| - | [[Category: Hsien, J H]] | + | [[Category: Hsien JH]] |
| - | [[Category: Shiau, A K]] | + | [[Category: Shiau AK]] |
| - | [[Category: Staszewski, L M]] | + | [[Category: Staszewski LM]] |
| - | [[Category: Coumarin]]
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| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Pde4b]]
| + | |
| Structural highlights
Function
PDE4B_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.[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
PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.
Water-soluble PDE4 inhibitors for the treatment of dry eye.,Govek SP, Oshiro G, Anzola JV, Beauregard C, Chen J, Coyle AR, Gamache DA, Hellberg MR, Hsien JN, Lerch JM, Liao JC, Malecha JW, Staszewski LM, Thomas DJ, Yanni JM, Noble SA, Shiau AK Bioorg Med Chem Lett. 2010 May 1;20(9):2928-32. Epub 2010 Mar 7. PMID:20378348[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xu RX, Hassell AM, Vanderwall D, Lambert MH, Holmes WD, Luther MA, Rocque WJ, Milburn MV, Zhao Y, Ke H, Nolte RT. Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. Science. 2000 Jun 9;288(5472):1822-5. PMID:10846163
- ↑ Xu RX, Rocque WJ, Lambert MH, Vanderwall DE, Luther MA, Nolte RT. Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J Mol Biol. 2004 Mar 19;337(2):355-65. PMID:15003452 doi:http://dx.doi.org/10.1016/j.jmb.2004.01.040
- ↑ Govek SP, Oshiro G, Anzola JV, Beauregard C, Chen J, Coyle AR, Gamache DA, Hellberg MR, Hsien JN, Lerch JM, Liao JC, Malecha JW, Staszewski LM, Thomas DJ, Yanni JM, Noble SA, Shiau AK. Water-soluble PDE4 inhibitors for the treatment of dry eye. Bioorg Med Chem Lett. 2010 May 1;20(9):2928-32. Epub 2010 Mar 7. PMID:20378348 doi:10.1016/j.bmcl.2010.03.023
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