2f3e: Difference between revisions
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<StructureSection load='2f3e' size='340' side='right'caption='[[2f3e]], [[Resolution|resolution]] 2.11Å' scene=''> | <StructureSection load='2f3e' size='340' side='right'caption='[[2f3e]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2f3e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2f3e]] is a 3 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=2F3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F3E FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AXQ:{(E)-(3R,6S,9R)-3-[(1S,3R)-3-((S)-1+-BUTYLCARBAMOYL-2-METHYL-PROPYLCARB+AMOYL)-1-HYDROXY-BUTYL]-6-METHYL-5,+8-DIOXO-1,11-DITHIA-4,7-DIAZA-CYCLO+PENTADEC-13-EN-9-YL}-CARBAMIC+ACID+TERT-BUTYL+ESTER'>AXQ</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AXQ:{(E)-(3R,6S,9R)-3-[(1S,3R)-3-((S)-1+-BUTYLCARBAMOYL-2-METHYL-PROPYLCARB+AMOYL)-1-HYDROXY-BUTYL]-6-METHYL-5,+8-DIOXO-1,11-DITHIA-4,7-DIAZA-CYCLO+PENTADEC-13-EN-9-YL}-CARBAMIC+ACID+TERT-BUTYL+ESTER'>AXQ</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=2f3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3e OCA], [https://pdbe.org/2f3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f3e RCSB], [https://www.ebi.ac.uk/pdbsum/2f3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f3e 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=2f3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3e OCA], [https://pdbe.org/2f3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f3e RCSB], [https://www.ebi.ac.uk/pdbsum/2f3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f3e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f3e_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f3e_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Rondeau J-M]] | |||
[[Category: Rondeau | |||
Latest revision as of 03:54, 21 November 2024
Crystal Structure of the Bace complex with AXQ093, a macrocyclic inhibitorCrystal Structure of the Bace complex with AXQ093, a macrocyclic inhibitor
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBased on the X-ray cocrystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM00-3), a series of macroheterocyclic analogues were designed and synthesized. Analogues containing dithia, dioxa, oxathia, and carbathia macrocycles were synthesized by methods relying on ring-closing olefin metathesis for the dioxa analogues and by alkylation of thiolates or bisthiolates for the others. Molecular modeling suggested that the incorporation of piperidine units appended to the macrocycles improved interactions through additional H-bonds and introduced further rigidity. These were synthesized in enantiomerically pure form using enzyme-catalyzed desymmetrization and diastereomer separation. Inhibitory activity on beta-site amyloid precursor protein cleaving enzyme (BACE) was observed with several macroheterocyclic inhibitors and structure-activity relationship (SAR) correlations were deduced. Cocrystal structures of two synthetic analogues revealed interesting and unexpected binding interactions. Structure-based design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease beta-site amyloid precursor protein cleaving enzyme (BACE).,Hanessian S, Yang G, Rondeau JM, Neumann U, Betschart C, Tintelnot-Blomley M J Med Chem. 2006 Jul 27;49(15):4544-67. PMID:16854060[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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