This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3hr1

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:3hr1.png|left|200px]]
+
==Discovery of novel inhibitors of PDE10A==
 +
<StructureSection load='3hr1' size='340' side='right' caption='[[3hr1]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3hr1]] is a 1 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HR1 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=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><br>
 +
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hqw|3hqw]], [[3hqy|3hqy]], [[3hqz|3hqz]]</td></tr>
 +
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pde10a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=3hr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hr1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hr1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hr1 PDBsum]</span></td></tr>
 +
<table>
 +
== 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/chain_selection.php?pdb_ID=2ata 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.
-
{{STRUCTURE_3hr1| PDB=3hr1 | SCENE= }}
+
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>
-
===Discovery of novel inhibitors of PDE10A===
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
{{ABSTRACT_PUBMED_19630403}}
+
-
 
+
-
==About this Structure==
+
-
[[3hr1]] is a 1 chain structure with 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].
+
==See Also==
==See Also==
*[[Phosphodiesterase|Phosphodiesterase]]
*[[Phosphodiesterase|Phosphodiesterase]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:019630403</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Marr, E S.]]
[[Category: Marr, E S.]]

Revision as of 12:51, 29 September 2014

Discovery of novel inhibitors of PDE10A

3hr1, resolution 1.53Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3hr1"
Views
Personal tools
Navigation
Toolbox