3g3n

<StructureSection load='3g3n' size='340' side='right' caption='[[3g3n]], [[Resolution|resolution]] 2.40&Aring;' scene=''>

<table><tr><td colspan='2'>[[3g3n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G3N FirstGlance]. <br>

</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TC8:3-(2,6-DIFLUOROPHENYL)-2-(METHYLTHIO)QUINAZOLIN-4(3H)-ONE'>TC8</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>

<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE7A, PDE7A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>

<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3g3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g3n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g3n RCSB], [http://www.ebi.ac.uk/pdbsum/3g3n PDBsum]</span></td></tr>

<table>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g3/3g3n_consurf.spt"</scriptWhenChecked>

</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

PDE7 inhibitors regulate pro-inflammatory and immune T-cell functions, and are a potentially novel class of drugs especially useful in the treatment of a wide variety of immune and inflammatory disorders. Starting from our lead family of thioxoquinazolines, we designed, synthesized, and characterized a novel series of thioxoquinazoline derivatives. Many of these compounds showed inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7A1 and at the micromolar level against PDE4D2. Cell-based studies showed that these compounds not only increased intracellular cAMP levels, but also had interesting anti-inflammatory properties within a therapeutic window. The in silico data predict that these compounds are capable of the crossing the blood-brain barrier. The X-ray crystal structure of the PDE7A1 catalytic domain in complex with compound 15 at a resolution of 2.4 A demonstrated that hydrophobic interactions at the active site pocket are a key feature. This structure, together with molecular modeling, provides insight into the selectivity of the PDE inhibitors and a template for the discovery of new PDE7 or PDE7/PDE4 dual inhibitors.

Synthesis, Structural Analysis, and Biological Evaluation of Thioxoquinazoline Derivatives as Phosphodiesterase 7 Inhibitors.,Castano T, Wang H, Campillo NE, Ballester S, Gonzalez-Garcia C, Hernandez J, Perez C, Cuenca J, Perez-Castillo A, Martinez A, Huertas O, Gelpi JL, Luque FJ, Ke H, Gil C ChemMedChem. 2009 Apr 6. PMID:19350606<ref>PMID:19350606</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

*[[Phosphodiesterase|Phosphodiesterase]]

[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]

[[Category: Castano, T.]]

[[Category: Wang, H.]]

[[Category: Camp]]

[[Category: Phosphoprotein]]