6b96: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 1: Line 1:


==Crystal Structure of PDE2 in complex with compound 16==
==Crystal Structure of PDE2 in complex with compound 16==
<StructureSection load='6b96' size='340' side='right' caption='[[6b96]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
<StructureSection load='6b96' size='340' side='right'caption='[[6b96]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6b96]] 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=6B96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B96 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6b96]] 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=6B96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B96 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CZV:6-chloro-N-{1-[4-(trifluoromethyl)phenyl]cyclopropyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine'>CZV</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.88&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CZV:6-chloro-N-{1-[4-(trifluoromethyl)phenyl]cyclopropyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine'>CZV</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6b96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b96 OCA], [https://pdbe.org/6b96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b96 RCSB], [https://www.ebi.ac.uk/pdbsum/6b96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b96 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=6b96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b96 OCA], [http://pdbe.org/6b96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b96 RCSB], [http://www.ebi.ac.uk/pdbsum/6b96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b96 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 ==
We have identified a novel PDE2 inhibitor series using fragment-based screening. Pyrazolopyrimidine fragment 1, while possessing weak potency (Ki=22.4muM), exhibited good binding efficiencies (LBE=0.49, LLE=4.48) to serve as a start for structure-based drug design. With the assistance of molecular modeling and X-ray crystallography, this fragment was developed into a series of potent PDE2 inhibitors with good physicochemical properties. Compound 16, a PDE2 selective inhibitor, was identified that exhibited favorable rat pharmacokinetic properties.


The identification of a novel lead class for phosphodiesterase 2 inhibition by fragment-based drug design.,Forster AB, Abeywickrema P, Bunda J, Cox CD, Cabalu TD, Egbertson M, Fay J, Getty K, Hall D, Kornienko M, Lu J, Parthasarathy G, Reid J, Sharma S, Shipe WD, Smith SM, Soisson S, Stachel SJ, Su HP, Wang D, Berger R Bioorg Med Chem Lett. 2017 Dec 1;27(23):5167-5171. doi:, 10.1016/j.bmcl.2017.10.054. Epub 2017 Oct 23. PMID:29113762<ref>PMID:29113762</ref>
==See Also==
 
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b96" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Lu, J]]
[[Category: Lu J]]
[[Category: Hydrolase]]
[[Category: Phosphodiesterase 2]]

Latest revision as of 17:32, 6 March 2024

Crystal Structure of PDE2 in complex with compound 16Crystal Structure of PDE2 in complex with compound 16

Structural highlights

6b96 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 1.88Å
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

6b96, resolution 1.88Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6b96&oldid=4083007"