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6a3n

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Revision as of 13:20, 10 May 2019

Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2

Structural highlights

6a3n is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	PDE9A (HUMAN)
Activity:	3',5'-cyclic-GMP phosphodiesterase, with EC number 3.1.4.35
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]

Publication Abstract from PubMed

To identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition.

Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.,Wu Y, Zhou Q, Zhang T, Li Z, Chen YP, Zhang P, Yu YF, Geng H, Tian YJ, Zhang C, Wang Y, Chen JW, Chen Y, Luo HB J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ Wu Y, Zhou Q, Zhang T, Li Z, Chen YP, Zhang P, Yu YF, Geng H, Tian YJ, Zhang C, Wang Y, Chen JW, Chen Y, Luo HB. Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia. J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01041

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6a3n"

@@ Line 3: / Line 3: @@
 <StructureSection load='6a3n' size='340' side='right'caption='[[6a3n]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6a3n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A3N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6a3n]] is a 2 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=6A3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A3N FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9Q9:1-cyclopentyl-6-({(2R)-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxopropan-2-yl}amino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one'>9Q9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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">PDE9A ([http://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'>[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=6a3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a3n OCA], [http://pdbe.org/6a3n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a3n RCSB], [http://www.ebi.ac.uk/pdbsum/6a3n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a3n ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: 3',5'-cyclic-GMP phosphodiesterase]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Chen, Y P]]

6a3n

From Proteopedia

Revision as of 13:20, 10 May 2019

Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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