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3h0e
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as Potent Non-Peptidic Inhibitors of Caspase-3== | |
| + | <StructureSection load='3h0e' size='340' side='right'caption='[[3h0e]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3h0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H0E FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H0E:(10S)-3,3-DIMETHYL-8-{[(2S)-2-(PHENOXYMETHYL)PYRROLIDIN-1-YL]SULFONYL}-2,3,4,10-TETRAHYDROPYRIMIDO[1,2-A]INDOL-10-OL'>H0E</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cp3|1cp3]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Caspase-3 Caspase-3], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.56 3.4.22.56] </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=3h0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h0e OCA], [https://pdbe.org/3h0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h0e RCSB], [https://www.ebi.ac.uk/pdbsum/3h0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h0e ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</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/h0/3h0e_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=3h0e ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cysteine-dependant aspartyl protease (caspase) activation has been implicated as a part of the signal transduction pathway leading to apoptosis. It has been postulated that caspase-3 inhibition could attenuate cell damage after an ischemic event and thereby providing for a novel neuroprotective treatment for stroke. As part of a program to develop a small molecule inhibitor of caspase-3, a novel series of 3,4-dihydropyrimido(1,2-a)indol-10(2H)-ones (pyrimidoindolones) was identified. The synthesis, biological evaluation and structure-activity relationships of the pyrimidoindolones are described. | ||
| - | + | 3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3.,Havran LM, Chong DC, Childers WE, Dollings PJ, Dietrich A, Harrison BL, Marathias V, Tawa G, Aulabaugh A, Cowling R, Kapoor B, Xu W, Mosyak L, Moy F, Hum WT, Wood A, Robichaud AJ Bioorg Med Chem. 2009 Nov 15;17(22):7755-68. Epub 2009 Sep 24. PMID:19836248<ref>PMID:19836248</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3h0e" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Caspase 3D structures|Caspase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Caspase-3]] | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Xu, W]] | ||
| + | [[Category: Apoptosis]] | ||
| + | [[Category: Cytoplasm]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Phosphoprotein]] | ||
| + | [[Category: Polymorphism]] | ||
| + | [[Category: Protease]] | ||
| + | [[Category: Protein-inhibitor complex]] | ||
| + | [[Category: S-nitrosylation]] | ||
| + | [[Category: Thiol protease]] | ||
| + | [[Category: Zymogen]] | ||
Current revision
3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as Potent Non-Peptidic Inhibitors of Caspase-3
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