6c7g: Difference between revisions

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 ==Crystal structure of human phosphodiesterase 2A with N-(1-adamantyl)-1-(2-chloro-5-isobutoxy-phenyl)-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-carboxamide==
-<StructureSection load='6c7g' size='340' side='right' caption='[[6c7g]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
+<StructureSection load='6c7g' size='340' side='right'caption='[[6c7g]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6c7g]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C7G FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6c7g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C7G FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EOY:1-[2-chloro-5-(2-methylpropoxy)phenyl]-4-methyl-N-[(3s,5s,7s)-tricyclo[3.3.1.1~3,7~]decan-1-yl][1,2,4]triazolo[4,3-a]quinoxaline-8-carboxamide'>EOY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.68&#8491;</td></tr>
-<tr id='activity'><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 id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EOY:1-[2-chloro-5-(2-methylpropoxy)phenyl]-4-methyl-N-[(3s,5s,7s)-tricyclo[3.3.1.1~3,7~]decan-1-yl][1,2,4]triazolo[4,3-a]quinoxaline-8-carboxamide'>EOY</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6c7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c7g OCA], [http://pdbe.org/6c7g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c7g RCSB], [http://www.ebi.ac.uk/pdbsum/6c7g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c7g ProSAT]</span></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=6c7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c7g OCA], [https://pdbe.org/6c7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c7g RCSB], [https://www.ebi.ac.uk/pdbsum/6c7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c7g ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>
+[https://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-In medicinal chemistry, additivity-based SAR analysis rests on three assumptions: (1) con-sistent binding pose of the central scaffold, (2) no interaction between the substitutions, and (3) a relatively rigid binding pocket in which the two substitutions act independently. Previously, non-additive SAR have been documented in systems that deviate from the first two assump-tions. Interestingly, protein structural change upon ligand binding, through induced fit or con-formational selection, although a well-known phenomenon that invalidates the third assump-tion, has not been linked to non-additive SAR conclusively. Here, for the first time, we show clear structural evidence that the formation of a hydrophobic pocket upon ligand binding in PDE2 catalytic site reduces the size of another distinct sub-pocket, and contribute to strong non-additive SAR between two otherwise distant R groups.
-Mathematical and Structural Characterization of Strong Non-additive SAR Caused by Protein Conformational Changes.,Gomez L, Xu R, Sinko W, Selfridge B, Vernier WF, Ly K, Truong R, Metz M, Marrone T, Sebring K, Yan Y, Appleton B, Aertgeerts K, Massari E, Breitenbucher JG J Med Chem. 2018 Aug 2. doi: 10.1021/acs.jmedchem.8b00713. PMID:30070482<ref>PMID:30070482</ref>
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6c7g" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
+[[Category: Homo sapiens]]
-[[Category: Aertgeerts, K]]
+[[Category: Large Structures]]
-[[Category: Xu, R]]
+[[Category: Aertgeerts K]]
-[[Category: Hydrolase]]
+[[Category: Xu R]]
-[[Category: Phosphodiesterase]]