|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4d08' size='340' side='right'caption='[[4d08]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4d08' size='340' side='right'caption='[[4d08]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4d08]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D08 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4d08]] 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=4D08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D08 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Q2T:1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8-(MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE'>Q2T</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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=Q2T:1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8-(MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE'>Q2T</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">[[4d09|4d09]]</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=4d08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d08 OCA], [https://pdbe.org/4d08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d08 RCSB], [https://www.ebi.ac.uk/pdbsum/4d08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d08 ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d08 OCA], [http://pdbe.org/4d08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d08 RCSB], [http://www.ebi.ac.uk/pdbsum/4d08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d08 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 20: |
| | | | |
| | ==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: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andres, J I]] | + | [[Category: Andres JI]] |
| - | [[Category: Buijnsters, P]] | + | [[Category: Buijnsters P]] |
| - | [[Category: DeAngelis, M]] | + | [[Category: DeAngelis M]] |
| - | [[Category: Langlois, X]] | + | [[Category: Langlois X]] |
| - | [[Category: Rombouts, F]] | + | [[Category: Rombouts F]] |
| - | [[Category: Sanderson, W]] | + | [[Category: Sanderson W]] |
| - | [[Category: Trabanco, A]] | + | [[Category: Trabanco A]] |
| - | [[Category: Tresadern, G]] | + | [[Category: Tresadern G]] |
| - | [[Category: VanHoof, G]] | + | [[Category: VanHoof G]] |
| - | [[Category: VanRoosbroeck, Y]] | + | [[Category: VanRoosbroeck Y]] |
| - | [[Category: Animal]]
| + | |
| - | [[Category: Binding site]]
| + | |
| - | [[Category: Catalytic domain]]
| + | |
| - | [[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]]
| + | |
| Structural highlights
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]
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 >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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ Buijnsters P, De Angelis M, Langlois X, Rombouts FJ, Sanderson W, Tresadern G, Ritchie A, Trabanco AA, VanHoof G, Roosbroeck YV, Andres JI. Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement. ACS Med Chem Lett. 2014 Jul 22;5(9):1049-53. doi: 10.1021/ml500262u. eCollection , 2014 Sep 11. PMID:25221665 doi:http://dx.doi.org/10.1021/ml500262u
|
