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[[Image:3gwt.png|left|200px]]


{{STRUCTURE_3gwt| PDB=3gwt | SCENE= }}  
==Catalytic domain of human phosphodiesterase 4B2B in complex with a quinoline inhibitor==
<StructureSection load='3gwt' size='340' side='right'caption='[[3gwt]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gwt]] 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=3GWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GWT 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=066:6-{[3-(DIMETHYLCARBAMOYL)PHENYL]SULFONYL}-4-[(3-METHOXYPHENYL)AMINO]-8-METHYLQUINOLINE-3-CARBOXAMIDE'>066</scene>, <scene name='pdbligand=ARS:ARSENIC'>ARS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3gwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gwt OCA], [https://pdbe.org/3gwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gwt RCSB], [https://www.ebi.ac.uk/pdbsum/3gwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gwt 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gw/3gwt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gwt ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-alpha from isolated human peripheral blood mononuclear cells with a pIC(50) of 11.1. GSK256066 also has a suitable profile for inhaled dosing.


===Catalytic domain of human phosphodiesterase 4B2B in complex with a quinoline inhibitor===
Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration.,Woodrow MD, Ballantine SP, Barker MD, Clarke BJ, Dawson J, Dean TW, Delves CJ, Evans B, Gough SL, Guntrip SB, Holman S, Holmes DS, Kranz M, Lindvaal MK, Lucas FS, Neu M, Ranshaw LE, Solanke YE, Somers DO, Ward P, Wiseman JO Bioorg Med Chem Lett. 2009 Sep 1;19(17):5261-5. Epub 2009 Apr 9. PMID:19656678<ref>PMID:19656678</ref>


{{ABSTRACT_PUBMED_19656678}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
==About this Structure==
<div class="pdbe-citations 3gwt" style="background-color:#fffaf0;"></div>
[[3gwt]] is a 1 chain structure of [[Phosphodiesterase]] 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=3GWT OCA].


==See Also==
==See Also==
*[[Phosphodiesterase|Phosphodiesterase]]
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:019656678</ref><references group="xtra"/>
__TOC__
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Neu, M.]]
[[Category: Large Structures]]
[[Category: Somers, D O.]]
[[Category: Neu M]]
[[Category: Camp]]
[[Category: Somers DO]]
[[Category: Hydrolase]]
[[Category: Pde]]
[[Category: Phosphodiesterase]]

Latest revision as of 10:13, 6 September 2023

Catalytic domain of human phosphodiesterase 4B2B in complex with a quinoline inhibitorCatalytic domain of human phosphodiesterase 4B2B in complex with a quinoline inhibitor

Structural highlights

3gwt is a 1 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 1.75Å
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]

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

Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-alpha from isolated human peripheral blood mononuclear cells with a pIC(50) of 11.1. GSK256066 also has a suitable profile for inhaled dosing.

Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration.,Woodrow MD, Ballantine SP, Barker MD, Clarke BJ, Dawson J, Dean TW, Delves CJ, Evans B, Gough SL, Guntrip SB, Holman S, Holmes DS, Kranz M, Lindvaal MK, Lucas FS, Neu M, Ranshaw LE, Solanke YE, Somers DO, Ward P, Wiseman JO Bioorg Med Chem Lett. 2009 Sep 1;19(17):5261-5. Epub 2009 Apr 9. PMID:19656678[3]

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Woodrow MD, Ballantine SP, Barker MD, Clarke BJ, Dawson J, Dean TW, Delves CJ, Evans B, Gough SL, Guntrip SB, Holman S, Holmes DS, Kranz M, Lindvaal MK, Lucas FS, Neu M, Ranshaw LE, Solanke YE, Somers DO, Ward P, Wiseman JO. Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5261-5. Epub 2009 Apr 9. PMID:19656678 doi:10.1016/j.bmcl.2009.04.012

3gwt, resolution 1.75Å

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