3frg

From Proteopedia

(Difference between revisions)

Current revision

Catalytic Domain of Human Phosphodiesterase 4B2B in Complex with a Quinoline Inhibitor

Structural highlights

3frg 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 1.7Å
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 a series of quinoline derivatives that were highly potent and selective inhibitors of PDE4 with a good pharmacokinetic profile in the rat. Quinolines 43 and 48 have potential as oral medicines for the treatment of COPD.

Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration.,Lunniss CJ, Cooper AW, Eldred CD, Kranz M, Lindvall M, Lucas FS, Neu M, Preston AG, Ranshaw LE, Redgrave AJ, Ed Robinson J, Shipley TJ, Solanke YE, Somers DO, Wiseman JO Bioorg Med Chem Lett. 2009 Mar 1;19(5):1380-5. Epub 2009 Jan 19. PMID:19195882^[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
↑ Lunniss CJ, Cooper AW, Eldred CD, Kranz M, Lindvall M, Lucas FS, Neu M, Preston AG, Ranshaw LE, Redgrave AJ, Ed Robinson J, Shipley TJ, Solanke YE, Somers DO, Wiseman JO. Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1380-5. Epub 2009 Jan 19. PMID:19195882 doi:10.1016/j.bmcl.2009.01.045

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Neu M | Somers DO

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 3frg is ON HOLD  until Jan 08 2011
+==Catalytic Domain of Human Phosphodiesterase 4B2B in Complex with a Quinoline Inhibitor==
+<StructureSection load='3frg' size='340' side='right'caption='[[3frg]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3frg]] 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=3FRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FRG 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]] 1.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=SK4:4-[(3-METHOXYPHENYL)AMINO]-6-(METHYLSULFONYL)QUINOLINE-3-CARBOXAMIDE'>SK4</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=3frg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3frg OCA], [https://pdbe.org/3frg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3frg RCSB], [https://www.ebi.ac.uk/pdbsum/3frg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3frg 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/fr/3frg_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=3frg 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 a series of quinoline derivatives that were highly potent and selective inhibitors of PDE4 with a good pharmacokinetic profile in the rat. Quinolines 43 and 48 have potential as oral medicines for the treatment of COPD.
-Authors: Somers, D.O., Neu, M.
+Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration.,Lunniss CJ, Cooper AW, Eldred CD, Kranz M, Lindvall M, Lucas FS, Neu M, Preston AG, Ranshaw LE, Redgrave AJ, Ed Robinson J, Shipley TJ, Solanke YE, Somers DO, Wiseman JO Bioorg Med Chem Lett. 2009 Mar 1;19(5):1380-5. Epub 2009 Jan 19. PMID:19195882<ref>PMID:19195882</ref>
-Description: Catalytic Domain of Human Phosphodiesterase 4B2B in Complex with a Quinoline Inhibitor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3frg" style="background-color:#fffaf0;"></div>
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar  4 14:41:37 2009''
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Neu M]]
+[[Category: Somers DO]]

3frg

From Proteopedia

Current revision

Catalytic Domain of Human Phosphodiesterase 4B2B in Complex with a Quinoline Inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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