1zkl

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[[Image:1zkl.gif|left|200px]]
 
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==Multiple Determinants for Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases==
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The line below this paragraph, containing "STRUCTURE_1zkl", creates the "Structure Box" on the page.
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<StructureSection load='1zkl' size='340' side='right'caption='[[1zkl]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1zkl]] 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=1ZKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZKL FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.67&#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=IBM:3-ISOBUTYL-1-METHYLXANTHINE'>IBM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1zkl| PDB=1zkl | SCENE= }}
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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=1zkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zkl OCA], [https://pdbe.org/1zkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zkl RCSB], [https://www.ebi.ac.uk/pdbsum/1zkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zkl ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PDE7A_HUMAN PDE7A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.<ref>PMID:19350606</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/zk/1zkl_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=1zkl ConSurf].
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<div style="clear:both"></div>
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'''Multiple Determinants for Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases'''
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==See Also==
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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==Overview==
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<references/>
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Phosphodiesterase (PDE) inhibitors have been widely studied as therapeutics for treatment of human diseases. However, the mechanism by which each PDE family recognizes selectively a category of inhibitors remains a puzzle. Here we report the crystal structure of PDE7A1 catalytic domain in complex with non-selective inhibitor 3-isobutyl-1-methylxanthine and kinetic analysis on the mutants of PDE7A1 and PDE4D2. Our studies suggest at least three elements play critical roles in inhibitor selectivity: 1) the conformation and position of an invariant glutamine, 2) the natures of scaffolding residues, and 3) residues that alter shape and size of the binding pocket. Kinetic analysis shows that single PDE7 to PDE4 mutations increase the sensitivity of PDE7 to PDE4 inhibitors but are not sufficient to render the engineered enzymes comparable with the wild types. The triple S373Y/S377T/I412S mutation of PDE7A1 produces a PDE4-like enzyme, implying that multiple elements must work together to determine inhibitor selectivity.
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__TOC__
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</StructureSection>
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==About this Structure==
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1ZKL 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=1ZKL OCA].
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==Reference==
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Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide phosphodiesterases 4 and 7., Wang H, Liu Y, Chen Y, Robinson H, Ke H, J Biol Chem. 2005 Sep 2;280(35):30949-55. Epub 2005 Jul 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15994308 15994308]
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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: Chen, Y.]]
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[[Category: Chen Y]]
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[[Category: Ke, H.]]
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[[Category: Ke H]]
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[[Category: Liu, Y.]]
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[[Category: Liu Y]]
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[[Category: Robinson, H.]]
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[[Category: Robinson H]]
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[[Category: Wang, H.]]
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[[Category: Wang H]]
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[[Category: Pde]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:44:29 2008''
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Current revision

Multiple Determinants for Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases

PDB ID 1zkl

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