3w5e

From Proteopedia

(Difference between revisions)

Current revision

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

Structural highlights

3w5e is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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. Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors. 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 doi:10.1016/j.bmcl.2013.03.104

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3w5e"

Categories: Homo sapiens | Large Structures | Hanzawa H | Takahashi M

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 3w5e is ON HOLD  until Paper Publication
+==Crystal structure of phosphodiesterase 4B in complex with compound 31e==
+<StructureSection load='3w5e' size='340' side='right'caption='[[3w5e]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<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>
+</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>
+<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>
+<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>
+</table>
+== Function ==
+[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+-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.
-Authors: Takahashi, M., Hanzawa, H.
+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>
-Description: Crystal structure of phosphodiesterase 4B in complex with compound 31e
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3w5e" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Hanzawa H]]
+[[Category: Takahashi M]]

3w5e

From Proteopedia

Current revision

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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