2fm0: Difference between revisions

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-[[Image:2fm0.gif|left|200px]]
-<!--
+==Crystal structure of PDE4D in complex with L-869298==
-The line below this paragraph, containing "STRUCTURE_2fm0", creates the "Structure Box" on the page.
+<StructureSection load='2fm0' size='340' side='right'caption='[[2fm0]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2fm0]] is a 4 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=2FM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FM0 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M98:(S)-3-(2-(3-CYCLOPROPOXY-4-(DIFLUOROMETHOXY)PHENYL)-2-(5-(1,1,1,3,3,3-HEXAFLUORO-2-HYDROXYPROPAN-2-YL)THIAZOL-2-YL)ETHYL)PYRIDINE+1-OXIDE'>M98</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_2fm0|  PDB=2fm0  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fm0 OCA], [https://pdbe.org/2fm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fm0 RCSB], [https://www.ebi.ac.uk/pdbsum/2fm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fm0 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.  Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</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/fm/2fm0_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=2fm0 ConSurf].
+<div style="clear:both"></div>
-'''Crystal structure of PDE4D in complex with L-869298'''
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
-==Overview==
+<references/>
-Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to preserve the pivotal interactions between the Mg-bound waters and the N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanations for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design.
+__TOC__
+</StructureSection>
-==About this Structure==
-FM0 is a [[Single protein]] structure of 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=2FM0 OCA].
-==Reference==
-Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase., Huai Q, Sun Y, Wang H, Macdonald D, Aspiotis R, Robinson H, Huang Z, Ke H, J Med Chem. 2006 Mar 23;49(6):1867-73. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16539372 16539372]
-[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Aspiotis, R.]]
+[[Category: Aspiotis R]]
-[[Category: Huai, Q.]]
+[[Category: Huai Q]]
-[[Category: Huang, Z.]]
+[[Category: Huang Z]]
-[[Category: Ke, H.]]
+[[Category: Ke H]]
-[[Category: Macdonald, D.]]
+[[Category: Macdonald D]]
-[[Category: Robinson, H.]]
+[[Category: Robinson H]]
-[[Category: Sun, Y.]]
+[[Category: Sun Y]]
-[[Category: Wang, H.]]
+[[Category: Wang H]]
-[[Category: Camp signalling]]
-[[Category: Crystal structure]]
-[[Category: Inhibitor selectivity]]
-[[Category: Pde. enantiomer binding]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 04:03:10 2008''