4gh6: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4gh6]] 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=4GH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GH6 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4gh6]] 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=4GH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GH6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LUO:N-(4-METHOXYPHENYL)-N~2~-[1-(2-METHYLPHENYL)-4-OXO-4,5-DIHYDRO-1H-PYRAZOLO[3,4-D]PYRIMIDIN-6-YL]-L-ALANINAMIDE'>LUO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LUO:N-(4-METHOXYPHENYL)-N~2~-[1-(2-METHYLPHENYL)-4-OXO-4,5-DIHYDRO-1H-PYRAZOLO[3,4-D]PYRIMIDIN-6-YL]-L-ALANINAMIDE'>LUO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4gh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gh6 OCA], [https://pdbe.org/4gh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gh6 RCSB], [https://www.ebi.ac.uk/pdbsum/4gh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gh6 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=4gh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gh6 OCA], [https://pdbe.org/4gh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gh6 RCSB], [https://www.ebi.ac.uk/pdbsum/4gh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gh6 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 ==
A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved the load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC(50) of 21 nM and 3.3 muM, respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors.
Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design.,Meng F, Hou J, Shao YX, Wu PY, Huang M, Zhu X, Cai Y, Li Z, Xu J, Liu P, Luo HB, Wan Y, Ke H J Med Chem. 2012 Oct 1. PMID:22985069<ref>PMID:22985069</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gh6" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 14:30, 1 March 2024

Crystal structure of the PDE9A catalytic domain in complex with inhibitor 28Crystal structure of the PDE9A catalytic domain in complex with inhibitor 28

Structural highlights

4gh6 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 2.7Å
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

4gh6, resolution 2.70Å

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