3w5e

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{{STRUCTURE_3w5e| PDB=3w5e | SCENE= }}
 
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===Crystal structure of phosphodiesterase 4B in complex with compound 31e===
 
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{{ABSTRACT_PUBMED_23602400}}
 
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==Function==
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==Crystal structure of phosphodiesterase 4B in complex with compound 31e==
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[[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>
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<StructureSection load='3w5e' size='340' side='right'caption='[[3w5e]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3w5e]] is a 2 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=3W5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W5E FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NVW:N-TERT-BUTYL-2-{4-[(5,5-DIOXIDO-2-PHENYL-7,8-DIHYDRO-6H-THIOPYRANO[3,2-D]PYRIMIDIN-4-YL)AMINO]PHENYL}ACETAMIDE'>NVW</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3w5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w5e OCA], [https://pdbe.org/3w5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w5e RCSB], [https://www.ebi.ac.uk/pdbsum/3w5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w5e ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50=25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50=7.5nM) and TNF-alpha production in mouse splenocytes (IC50=9.8nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50=18mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex.
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==About this Structure==
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Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.,Goto T, Shiina A, Yoshino T, Mizukami K, Hirahara K, Suzuki O, Sogawa Y, Takahashi T, Mikkaichi T, Nakao N, Takahashi M, Hasegawa M, Sasaki S Bioorg Med Chem Lett. 2013 Jun 1;23(11):3325-8. doi: 10.1016/j.bmcl.2013.03.104. , Epub 2013 Apr 4. PMID:23602400<ref>PMID:23602400</ref>
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[[3w5e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W5E OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:023602400</ref><references group="xtra"/><references/>
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</div>
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[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
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<div class="pdbe-citations 3w5e" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hanzawa, H.]]
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[[Category: Large Structures]]
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[[Category: Takahashi, M.]]
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[[Category: Hanzawa H]]
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[[Category: Copd]]
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[[Category: Takahashi M]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Inhibitor]]
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[[Category: Phosphodiesterase]]
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Current revision

Crystal structure of phosphodiesterase 4B in complex with compound 31e

PDB ID 3w5e

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