4nw7: Difference between revisions
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''' | ==PDE4 catalytic domain== | ||
<StructureSection load='4nw7' size='340' side='right' caption='[[4nw7]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4nw7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NW7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NW7 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2O5:(4-{[4-(3-CHLOROPHENYL)-6-CYCLOPROPYL-1,3,5-TRIAZIN-2-YL]AMINO}PHENYL)ACETIC+ACID'>2O5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nw7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nw7 RCSB], [http://www.ebi.ac.uk/pdbsum/4nw7 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both catalytic domain and CR3 residues. This provides the first structure-based approach to engineer PDE4B-selective inhibitors. | |||
Discovery of triazines as selective PDE4B versus PDE4D inhibitors.,Hagen TJ, Mo X, Burgin AB, Fox D 3rd, Zhang Z, Gurney ME Bioorg Med Chem Lett. 2014 Aug 15;24(16):4031-4. doi: 10.1016/j.bmcl.2014.06.002., Epub 2014 Jun 12. PMID:24998378<ref>PMID:24998378</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | |||
[[Category: Edwards, T E.]] | |||
[[Category: III, D Fox.]] | |||
[[Category: Catalytic]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Pde4]] | |||
[[Category: Phosphodiesterase]] | |||
Revision as of 13:36, 20 October 2014
PDE4 catalytic domainPDE4 catalytic domain
Structural highlights
Publication Abstract from PubMedIn this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both catalytic domain and CR3 residues. This provides the first structure-based approach to engineer PDE4B-selective inhibitors. Discovery of triazines as selective PDE4B versus PDE4D inhibitors.,Hagen TJ, Mo X, Burgin AB, Fox D 3rd, Zhang Z, Gurney ME Bioorg Med Chem Lett. 2014 Aug 15;24(16):4031-4. doi: 10.1016/j.bmcl.2014.06.002., Epub 2014 Jun 12. PMID:24998378[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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