4d09: Difference between revisions

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==PDE2a catalytic domain in complex with a brain penetrant inhibitor==
==PDE2a catalytic domain in complex with a brain penetrant inhibitor==
<StructureSection load='4d09' size='340' side='right' caption='[[4d09]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='4d09' size='340' side='right'caption='[[4d09]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4d09]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D09 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D09 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4d09]] is a 4 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=4D09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D09 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=788:N-BENZYL-4-METHYL-1-PHENYL[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE-8-CARBOXAMIDE'>788</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]] 2.5&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d08|4d08]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=788:N-BENZYL-4-METHYL-1-PHENYL[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE-8-CARBOXAMIDE'>788</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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-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] </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=4d09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d09 OCA], [https://pdbe.org/4d09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d09 RCSB], [https://www.ebi.ac.uk/pdbsum/4d09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d09 ProSAT]</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=4d09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d09 OCA], [http://pdbe.org/4d09 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d09 RCSB], [http://www.ebi.ac.uk/pdbsum/4d09 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d09 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref> 
[https://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a &gt;210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 muM. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders.
 
Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement.,Buijnsters P, De Angelis M, Langlois X, Rombouts FJ, Sanderson W, Tresadern G, Ritchie A, Trabanco AA, VanHoof G, Roosbroeck YV, Andres JI ACS Med Chem Lett. 2014 Jul 22;5(9):1049-53. doi: 10.1021/ml500262u. eCollection , 2014 Sep 11. PMID:25221665<ref>PMID:25221665</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4d09" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Phosphodiesterase|Phosphodiesterase]]
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Andres, J I]]
[[Category: Large Structures]]
[[Category: Buijnsters, P]]
[[Category: Andres JI]]
[[Category: DeAngelis, M]]
[[Category: Buijnsters P]]
[[Category: Langlois, X]]
[[Category: DeAngelis M]]
[[Category: Rombouts, F]]
[[Category: Langlois X]]
[[Category: Sanderson, W]]
[[Category: Rombouts F]]
[[Category: Trabanco, A]]
[[Category: Sanderson W]]
[[Category: Tresadern, G]]
[[Category: Trabanco A]]
[[Category: VanHoof, G]]
[[Category: Tresadern G]]
[[Category: VanRoosbroeck, Y]]
[[Category: VanHoof G]]
[[Category: Animal]]
[[Category: VanRoosbroeck Y]]
[[Category: Cyclic nucleotide phosphodiesterase]]
[[Category: Disease model]]
[[Category: Drug evaluation]]
[[Category: Hydrolase]]
[[Category: Phosphodiesterase 2 inhibitor]]
[[Category: Phosphodiesterase inhibitor]]
[[Category: Preclinical]]
[[Category: Protein binding]]
[[Category: Structure-activity relationship]]
[[Category: Type 2]]
[[Category: Type 4]]

Latest revision as of 10:19, 1 May 2024

PDE2a catalytic domain in complex with a brain penetrant inhibitorPDE2a catalytic domain in complex with a brain penetrant inhibitor

Structural highlights

4d09 is a 4 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 2.5Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE2A_HUMAN Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.[1] [2]

See Also

References

  1. ↑ Iffland A, Kohls D, Low S, Luan J, Zhang Y, Kothe M, Cao Q, Kamath AV, Ding YH, Ellenberger T. Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system. Biochemistry. 2005 Jun 14;44(23):8312-25. PMID:15938621 doi:10.1021/bi047313h
  2. ↑ Pandit J, Forman MD, Fennell KF, Dillman KS, Menniti FS. Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct. Proc Natl Acad Sci U S A. 2009 Oct 14. PMID:19828435

4d09, resolution 2.50Å

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