3qpp: Difference between revisions
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==Structure of PDE10-inhibitor complex== | ==Structure of PDE10-inhibitor complex== | ||
<StructureSection load='3qpp' size='340' side='right' caption='[[3qpp]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='3qpp' size='340' side='right' caption='[[3qpp]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3qpp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3qpp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QPP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QPP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PFW:7-METHOXY-4-[(3S)-3-PHENYLPIPERIDIN-1-YL]-6-[2-(QUINOLIN-2-YL)ETHOXY]QUINAZOLINE'>PFW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PFW:7-METHOXY-4-[(3S)-3-PHENYLPIPERIDIN-1-YL]-6-[2-(QUINOLIN-2-YL)ETHOXY]QUINAZOLINE'>PFW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o8h|2o8h]], [[2ovv|2ovv]], [[2ovy|2ovy]], [[3qpn|3qpn]], [[3qpo|3qpo]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o8h|2o8h]], [[2ovv|2ovv]], [[2ovy|2ovy]], [[3qpn|3qpn]], [[3qpo|3qpo]]</td></tr> | ||
<tr id='gene'><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 | <tr id='gene'><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 Buffalo rat])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qpp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qpp RCSB], [http://www.ebi.ac.uk/pdbsum/3qpp PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qpp OCA], [http://pdbe.org/3qpp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qpp RCSB], [http://www.ebi.ac.uk/pdbsum/3qpp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qpp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3qpp" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Buffalo rat]] | ||
[[Category: Marr, E S]] | [[Category: Marr, E S]] | ||
[[Category: Pandit, J]] | [[Category: Pandit, J]] | ||
Revision as of 23:30, 4 August 2016
Structure of PDE10-inhibitor complexStructure of PDE10-inhibitor complex
Structural highlights
Function[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.[1] Publication Abstract from PubMedUtilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability. Use of Structure-Based Design to Discover a Potent, Selective, In Vivo Active Phosphodiesterase 10A Inhibitor Lead Series for the Treatment of Schizophrenia.,Helal CJ, Kang Z, Hou X, Pandit J, Chappie TA, Humphrey JM, Marr ES, Fennell KF, Chenard LK, Fox C, Schmidt CJ, Williams RD, Chapin DS, Siuciak J, Lebel L, Menniti F, Cianfrogna J, Fonseca KR, Nelson FR, O'Connor R, Macdougall M, McDowell L, Liras S J Med Chem. 2011 Jun 8. PMID:21650160[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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