3qi3: Difference between revisions

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<StructureSection load='3qi3' size='340' side='right'caption='[[3qi3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='3qi3' size='340' side='right'caption='[[3qi3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3qi3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QI3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3qi3]] 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=3QI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QI3 FirstGlance]. <br>
</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=PDB:1-(2-CHLOROPHENYL)-6-[(2R)-3,3,3-TRIFLUORO-2-METHYLPROPYL]-1,7-DIHYDRO-4H-PYRAZOLO[3,4-D]PYRIMIDIN-4-ONE'>PDB</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]] 2.3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qi4|3qi4]]</div></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=PDB:1-(2-CHLOROPHENYL)-6-[(2R)-3,3,3-TRIFLUORO-2-METHYLPROPYL]-1,7-DIHYDRO-4H-PYRAZOLO[3,4-D]PYRIMIDIN-4-ONE'>PDB</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">PDE, PDE9A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3',5'-cyclic-GMP_phosphodiesterase 3',5'-cyclic-GMP phosphodiesterase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qi3 OCA], [https://pdbe.org/3qi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qi3 RCSB], [https://www.ebi.ac.uk/pdbsum/3qi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qi3 ProSAT]</span></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=3qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qi3 OCA], [https://pdbe.org/3qi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qi3 RCSB], [https://www.ebi.ac.uk/pdbsum/3qi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qi3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/PDE9A_HUMAN PDE9A_HUMAN]] Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.<ref>PMID:18757755</ref> 
[https://www.uniprot.org/uniprot/PDE9A_HUMAN PDE9A_HUMAN] Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.<ref>PMID:18757755</ref>  
<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.
 
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>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3qi3" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 3',5'-cyclic-GMP phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[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: Glutamine switch]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Mutation]]

Latest revision as of 13:48, 21 February 2024

Crystal structure of PDE9A(Q453E) in complex with inhibitor BAY73-6691Crystal structure of PDE9A(Q453E) in complex with inhibitor BAY73-6691

Structural highlights

3qi3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE9A_HUMAN Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.[1]

See Also

References

  1. ↑ Liu S, Mansour MN, Dillman KS, Perez JR, Danley DE, Aeed PA, Simons SP, Lemotte PK, Menniti FS. Structural basis for the catalytic mechanism of human phosphodiesterase 9. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13309-14. Epub 2008 Aug 29. PMID:18757755

3qi3, resolution 2.30Å

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