4ke0: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 4ke0 is ON HOLD
+==Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 13==
+<StructureSection load='4ke0' size='340' side='right'caption='[[4ke0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ke0]] 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=4KE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KE0 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1R8:(3S)-3-[(1R)-2-{[(4S)-6-ETHYL-3,4-DIHYDROSPIRO[CHROMENE-2,1-CYCLOBUTAN]-4-YL]AMINO}-1-HYDROXYETHYL]-4-AZABICYCLO[10.3.1]HEXADECA-1(16),12,14-TRIEN-5-ONE'>1R8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4ke0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ke0 OCA], [https://pdbe.org/4ke0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ke0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ke0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ke0 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+We describe a systematic study of how macrocyclization in the P1-P3 region of hydroxyethylamine-based inhibitors of beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE1) modulates in vitro activity. This study reveals that in a number of instances macrocyclization of bis-terminal dienes leads to improved potency toward BACE1 and selectivity against cathepsin D (CatD), as well as greater amyloid beta-peptide (Abeta)-lowering activity in HEK293T cells stably expressing APPSW. However, for several closely related analogs the benefits of macrocyclization are attenuated by the effects of other structural features in different regions of the molecules. X-ray crystal structures of three of these novel macrocyclic inhibitors bound to BACE1 revealed their binding conformations and interactions with the enzyme.
-Authors: Whittington, D.A., Long, A.M., Li, V.
+Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity.,Pennington LD, Whittington DA, Bartberger MD, Jordan SR, Monenschein H, Nguyen TT, Yang BH, Xue QM, Vounatsos F, Wahl RC, Chen K, Wood S, Citron M, Patel VF, Hitchcock SA, Zhong W Bioorg Med Chem Lett. 2013 Aug 1;23(15):4459-64. doi: 10.1016/j.bmcl.2013.05.028., Epub 2013 May 16. PMID:23769639<ref>PMID:23769639</ref>
-Description: Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 13
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ke0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Li V]]
+[[Category: Long AM]]
+[[Category: Whittington DA]]