3qi4: Difference between revisions

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-[[Image:3qi4.png|left|200px]]
+==Crystal structure of PDE9A(Q453E) in complex with IBMX==
+<StructureSection load='3qi4' size='340' side='right' caption='[[3qi4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3qi4]] is a 2 chain structure with 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=3QI4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QI4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qi3|3qi3]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE9A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-GMP_phosphodiesterase 3',5'-cyclic-GMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.35 3.1.4.35] </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=3qi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qi4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qi4 RCSB], [http://www.ebi.ac.uk/pdbsum/3qi4 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+PDE9 inhibitors show potential for treatment of diseases such as diabetes. To help with discovery of PDE9 inhibitors, we performed mutagenesis, kinetic, crystallographic, and molecular dynamics analyses on the active site residues of Gln453 and its stabilizing partner Glu406. The crystal structures of the PDE9 Q453E mutant (PDE9Q453E) in complex with inhibitors IBMX and (S)-BAY73-6691 showed asymmetric binding of the inhibitors in two subunits of the PDE9Q453E dimer and also the significant positional change of the M-loop at the active site. The kinetic analysis of the Q453E and E406A mutants suggested that the invariant glutamine is critical for binding of substrates and inhibitors, but is unlikely to play a key role in the differentiation between substrates of cGMP and cAMP. The molecular dynamics simulations suggest that residue Glu406 may be protonated and may thus explain the hydrogen bond distance between two side chain oxygens of Glu453 and Glu406 in the crystal structure of the PDE9Q453E mutant. The information from these studies may be useful for design of PDE9 inhibitors.
-{{STRUCTURE_3qi4|  PDB=3qi4  |  SCENE=  }}
+Structural asymmetry of phosphodiesterase-9, potential protonation of a glutamic Acid, and role of the invariant glutamine.,Hou J, Xu J, Liu M, Zhao R, Luo HB, Ke H PLoS One. 2011 Mar 31;6(3):e18092. PMID:21483814<ref>PMID:21483814</ref>
-===Crystal structure of PDE9A(Q453E) in complex with IBMX===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_21483814}}
-==About this Structure==
-[[3qi4]] is a 2 chain structure with 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=3QI4 OCA].
 ==See Also==
 *[[Phosphodiesterase|Phosphodiesterase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:021483814</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: 3',5'-cyclic-GMP phosphodiesterase]]
 [[Category: Homo sapiens]]
-[[Category: Hou, J.]]
+[[Category: Hou, J]]
-[[Category: Ke, H.]]
+[[Category: Ke, H]]
-[[Category: Liu, M.]]
+[[Category: Liu, M]]
-[[Category: Lou, H.]]
+[[Category: Lou, H]]
-[[Category: Xu, J.]]
+[[Category: Xu, J]]
-[[Category: Zhao, R.]]
+[[Category: Zhao, R]]
 [[Category: Hydrolase]]
 [[Category: Pde]]