2o8h

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:28, 3 April 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2o8h.gif|left|200px]]<br /><applet load="2o8h" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2o8h, resolution 1.800&Aring;" />
 
-
'''Crystal structure of the catalytic domain of rat phosphodiesterase 10A'''<br />
 
-
==Overview==
+
==Crystal structure of the catalytic domain of rat phosphodiesterase 10A==
-
A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.
+
<StructureSection load='2o8h' size='340' side='right'caption='[[2o8h]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2o8h]] 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=2O8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O8H 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]] 1.8&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=227:6,7-DIMETHOXY-4-{8-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-3,4-DIHYDROISOQUINOLIN-2(1H)-YL}QUINAZOLINE'>227</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2o8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o8h OCA], [https://pdbe.org/2o8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o8h RCSB], [https://www.ebi.ac.uk/pdbsum/2o8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o8h 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/o8/2o8h_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=2o8h ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
2O8H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=227:'>227</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O8H OCA].
+
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors., Chappie TA, Humphrey JM, Allen MP, Estep KG, Fox CB, Lebel LA, Liras S, Marr ES, Menniti FS, Pandit J, Schmidt CJ, Tu M, Williams RD, Yang FV, J Med Chem. 2007 Jan 25;50(2):182-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17228859 17228859]
+
__TOC__
-
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
+
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
-
[[Category: Single protein]]
+
[[Category: Marr ES]]
-
[[Category: Marr, E S.]]
+
[[Category: Pandit J]]
-
[[Category: Pandit, J.]]
+
-
[[Category: 227]]
+
-
[[Category: MG]]
+
-
[[Category: ZN]]
+
-
[[Category: phosphodiesterase 10a; zn-binding site]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:15:41 2008''
+

Current revision

Crystal structure of the catalytic domain of rat phosphodiesterase 10A

PDB ID 2o8h

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/2o8h"
Personal tools