3o57: Difference between revisions
New page: '''Unreleased structure''' The entry 3o57 is ON HOLD Authors: Somers, D.O., Neu, M. Description: Catalytic domain of human phosphodiesterase 4b2b in complex with a 5-heterocycle pyrazo... |
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==Catalytic domain of human phosphodiesterase 4b2b in complex with a 5-heterocycle pyrazolopyridine inhibitor== | |||
<StructureSection load='3o57' size='340' side='right'caption='[[3o57]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o57]] is a 1 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=3O57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O57 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARS:ARSENIC'>ARS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZG2:5-[5-BENZYL-4-(2-OXO-2-PYRROLIDIN-1-YLETHYL)-1,3-OXAZOL-2-YL]-1-ETHYL-N-(TETRAHYDRO-2H-PYRAN-4-YL)-1H-PYRAZOLO[3,4-B]PYRIDIN-4-AMINE'>ZG2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3o57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o57 OCA], [https://pdbe.org/3o57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o57 RCSB], [https://www.ebi.ac.uk/pdbsum/3o57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o57 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PDE4B_HUMAN PDE4B_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-alpha production from isolated human peripheral blood mononuclear cells. | |||
Pyrazolopyridines as potent PDE4B inhibitors: 5-heterocycle SAR.,Mitchell CJ, Ballantine SP, Coe DM, Cook CM, Delves CJ, Dowle MD, Edlin CD, Hamblin JN, Holman S, Johnson MR, Jones PS, Keeling SE, Kranz M, Lindvall M, Lucas FS, Neu M, Solanke YE, Somers DO, Trivedi NA, Wiseman JO Bioorg Med Chem Lett. 2010 Oct 1;20(19):5803-6. Epub 2010 Aug 5. PMID:20732811<ref>PMID:20732811</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3o57" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Neu M]] | |||
[[Category: Somers DO]] | |||