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6acb

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Revision as of 08:28, 10 October 2018

Crystal structure of PDE5 in complex with inhibitor LW1805

Structural highlights

6acb is a 1 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:	PDE5A, PDE5 (HUMAN)
Activity:	3',5'-cyclic-GMP phosphodiesterase, with EC number 3.1.4.35
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PDE5A_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.

Publication Abstract from PubMed

To further explore the structure-activity relationship around the chromeno[2,3- c]pyrrol-9(2 H)-one scaffold, 19 derivatives as inhibitors against PDE5 were discovered. The most potent inhibitor 3 has an IC50 of 0.32 nM with remarkable selectivity and druglike profile. Oral administration of 3 (1.25 mg/kg) caused comparable therapeutic effects to sildenafil (10.0 mg/kg) against pulmonary arterial hypertension. Further, different binding patterns from sildenafil were revealed in cocrystal structures, which provide structural templates for discovery of highly potent PDE5 inhibitors.

Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension.,Wu D, Huang Y, Chen Y, Huang YY, Geng H, Zhang T, Zhang C, Li Z, Guo L, Chen J, Luo HB J Med Chem. 2018 Sep 7. doi: 10.1021/acs.jmedchem.8b01209. PMID:30148362^[1]

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

References

↑ Wu D, Huang Y, Chen Y, Huang YY, Geng H, Zhang T, Zhang C, Li Z, Guo L, Chen J, Luo HB. Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension. J Med Chem. 2018 Sep 7. doi: 10.1021/acs.jmedchem.8b01209. PMID:30148362 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01209

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/6acb"

@@ Line 3: / Line 3: @@
 <StructureSection load='6acb' size='340' side='right' caption='[[6acb]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6acb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ACB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ACB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6acb]] is a 1 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=6ACB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ACB FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9T9:3-[(2H-1,3-benzodioxol-5-yl)methyl]-8-fluoro-6-{[2-(4-methylpiperazin-1-yl)ethyl]amino}-1-(1,3-thiazol-2-yl)[1]benzopyrano[2,3-c]pyrrol-9(2H)-one'>9T9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">PDE5A, PDE5 ([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=6acb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6acb OCA], [http://pdbe.org/6acb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6acb RCSB], [http://www.ebi.ac.uk/pdbsum/6acb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6acb ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: 3',5'-cyclic-GMP phosphodiesterase]]
+[[Category: Human]]
 [[Category: Huang, Y D]]
 [[Category: Huang, Y Y]]

6acb

From Proteopedia

Revision as of 08:28, 10 October 2018

Crystal structure of PDE5 in complex with inhibitor LW1805

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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