1q9m

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[[Image:1q9m.jpg|left|200px]]<br /><applet load="1q9m" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1q9m, resolution 2.3&Aring;" />
 
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'''Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity'''<br />
 
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==Overview==
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==Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity==
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Selective inhibitors against the 11 families of cyclic nucleotide phosphodiesterases (PDEs) are used to treat various human diseases. How the inhibitors selectively bind the conserved PDE catalytic domains is unknown. The crystal structures of the PDE4D2 catalytic domain in complex with (R)- or (R,S)-rolipram suggest that inhibitor selectivity is determined by the chemical nature of amino acids and subtle conformational changes of the binding pockets. The conformational states of Gln369 in PDE4D2 may play a key role in inhibitor recognition. The corresponding Y329S mutation in PDE7 may lead to loss of the hydrogen bonds between rolipram and Gln369 and is thus a possible reason explaining PDE7's insensitivity to rolipram inhibition. Docking of the PDE5 inhibitor sildenafil into the PDE4 catalytic pocket further helps understand inhibitor selectivity.
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<StructureSection load='1q9m' size='340' side='right'caption='[[1q9m]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1q9m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1oym 1oym]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q9M FirstGlance]. <br>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ROL:ROLIPRAM'>ROL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q9m OCA], [https://pdbe.org/1q9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q9m RCSB], [https://www.ebi.ac.uk/pdbsum/1q9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q9m ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q9/1q9m_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1q9m ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600129 600129]]
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1Q9M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=ROL:'>ROL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1OYM. Active as [http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q9M OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity., Huai Q, Wang H, Sun Y, Kim HY, Liu Y, Ke H, Structure. 2003 Jul;11(7):865-73. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12842049 12842049]
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[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Huai, Q.]]
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[[Category: Huai Q]]
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[[Category: Ke, H.]]
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[[Category: Ke H]]
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[[Category: Kim, H Y.]]
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[[Category: Kim HY]]
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[[Category: Liu, Y.]]
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[[Category: Liu Y]]
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[[Category: Sun, Y.]]
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[[Category: Sun Y]]
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[[Category: Wang, H.]]
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[[Category: Wang H]]
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[[Category: ROL]]
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[[Category: ZN]]
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[[Category: pde]]
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[[Category: rolipram]]
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[[Category: specific inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:21 2008''
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Current revision

Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity

PDB ID 1q9m

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