2qyk: Difference between revisions

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OCA

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 ==Crystal structure of PDE4A10 in complex with inhibitor NPV==
-<StructureSection load='2qyk' size='340' side='right' caption='[[2qyk]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='2qyk' size='340' side='right'caption='[[2qyk]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2qyk]] is a 2 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=2QYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QYK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2qyk]] 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=2QYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QYK 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=NPV:4-[8-(3-NITROPHENYL)-1,7-NAPHTHYRIDIN-6-YL]BENZOIC+ACID'>NPV</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]] 2.1&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qyl|2qyl]], [[2qym|2qym]], [[2qyn|2qyn]]</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=NPV:4-[8-(3-NITROPHENYL)-1,7-NAPHTHYRIDIN-6-YL]BENZOIC+ACID'>NPV</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">PDE4A ([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=2qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qyk OCA], [https://pdbe.org/2qyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qyk RCSB], [https://www.ebi.ac.uk/pdbsum/2qyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qyk ProSAT]</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=2qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qyk OCA], [http://pdbe.org/2qyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qyk RCSB], [http://www.ebi.ac.uk/pdbsum/2qyk PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</ref>
+[https://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</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/qy/2qyk_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qy/2qyk_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 20: / Line 20: @@
 </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=2qyk ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-PDE4 (phosphodiesterase-4)-selective inhibitors have attracted much attention as potential therapeutics for the treatment of both depression and major inflammatory diseases, but their practical application has been compromised by side effects. A possible cause for the side effects is that current PDE4-selective inhibitors similarly inhibit isoforms from all four PDE4 subfamilies. The development of PDE4 subfamily-selective inhibitors has been hampered by a lack of structural information. In the present study, we rectify this by providing the crystal structures of the catalytic domains of PDE4A, PDE4B and PDE4D in complex with the PDE4 inhibitor NVP {4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid} as well as the unliganded PDE4C structure. NVP binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. However, detailed structural comparison reveals significant conformational differences. Although the active sites of PDE4B and PDE4D are mostly comparable, PDE4A shows significant displacements of the residues next to the invariant glutamine residue that is critical for substrate and inhibitor binding. PDE4C appears to be more distal from other PDE4 subfamilies, with certain key residues being disordered. Our analyses provide the first structural basis for the development of PDE4 subfamily-selective inhibitors.
-Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors.,Wang H, Peng MS, Chen Y, Geng J, Robinson H, Houslay MD, Cai J, Ke H Biochem J. 2007 Dec 1;408(2):193-201. PMID:17727341<ref>PMID:17727341</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 2qyk" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Phosphodiesterase|Phosphodiesterase]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Chen, Y]]
+[[Category: Large Structures]]
-[[Category: Geng, J]]
+[[Category: Chen Y]]
-[[Category: Houslay, M]]
+[[Category: Geng J]]
-[[Category: Peng, M]]
+[[Category: Houslay M]]
-[[Category: Robinson, H]]
+[[Category: Peng M]]
-[[Category: Wang, H]]
+[[Category: Robinson H]]
-[[Category: Hydrolase]]
+[[Category: Wang H]]
-[[Category: Pde4 inhibitor]]
-[[Category: Subfamily inhibitor selectivity]]