3hr1: Difference between revisions

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-{{Seed}}
-[[Image:3hr1.jpg|left|200px]]
-<!--
+==Discovery of novel inhibitors of PDE10A==
-The line below this paragraph, containing "STRUCTURE_3hr1", creates the "Structure Box" on the page.
+<StructureSection load='3hr1' size='340' side='right'caption='[[3hr1]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3hr1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HR1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HR1 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.53&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PF9:2-{[4-(1-METHYL-4-PYRIDIN-4-YL-1H-PYRAZOL-3-YL)PHENOXY]METHYL}QUINOLINE'>PF9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3hr1|  PDB=3hr1  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hr1 OCA], [https://pdbe.org/3hr1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hr1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hr1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hr1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PDE10_RAT PDE10_RAT] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:10583409</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/3hr1_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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/main_output.php?pdb_ID=3hr1 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+By utilizing structure-based drug design (SBDD) knowledge, a novel class of phosphodiesterase (PDE) 10A inhibitors was identified. The structure-based drug design efforts identified a unique "selectivity pocket" for PDE10A inhibitors, and interactions within this pocket allowed the design of highly selective and potent PDE10A inhibitors. Further optimization of brain penetration and drug-like properties led to the discovery of 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920). This PDE10A inhibitor is the first reported clinical entry for this mechanism in the treatment of schizophrenia.
-===Discovery of novel inhibitors of PDE10A===
+Discovery of a Novel Class of Phosphodiesterase 10A Inhibitors and Identification of Clinical Candidate 2-[4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the Treatment of Schizophrenia (dagger) dagger Coordinates of the PDE10A crystal structures have been deposited in the Protein Data Bank for compound 1 (3HQW), 2 (3HQY), 3 (3HQW) and 9 (3HR1).,Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O'Connor R, Pandit J, Proulx-Lafrance C, Schmidt AW, Schmidt CJ, Suiciak JA, Liras S J Med Chem. 2009 Jul 24. PMID:19630403<ref>PMID:19630403</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3hr1" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-HR1 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HR1 OCA].
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Rattus norvegicus]]
-[[Category: Marr, E S.]]
+[[Category: Marr ES]]
-[[Category: Pandit, J.]]
+[[Category: Pandit J]]
-[[Category: Allosteric enzyme]]
-[[Category: Alternative splicing]]
-[[Category: Camp]]
-[[Category: Camp-binding]]
-[[Category: Cgmp]]
-[[Category: Cgmp-binding]]
-[[Category: Cytoplasm]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase/hydrolase inhibitor complex]]
-[[Category: Magnesium]]
-[[Category: Metal-binding]]
-[[Category: Nucleotide-binding]]
-[[Category: Pde 10a]]
-[[Category: Pde10 inhibitor]]
-[[Category: Phosphodiesterase 10a]]
-[[Category: Zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug  5 11:02:49 2009''