4ke1: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 19== | ==Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 19== | ||
<StructureSection load='4ke1' size='340' side='right' caption='[[4ke1]], [[Resolution|resolution]] 1.91Å' scene=''> | <StructureSection load='4ke1' size='340' side='right'caption='[[4ke1]], [[Resolution|resolution]] 1.91Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ke1]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4ke1]] is a 1 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=4KE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KE1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1R6:(12S)-12-[(1R)-2-{[(4S)-6-ETHYL-3,4-DIHYDROSPIRO[CHROMENE-2,1-CYCLOBUTAN]-4-YL]AMINO}-1-HYDROXYETHYL]-1,13-DIAZATRICYCLO[13.3.1.1~6,10~]ICOSA-6(20),7,9,15(19),16-PENTAENE-14,18-DIONE'>1R6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 1.91Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1R6:(12S)-12-[(1R)-2-{[(4S)-6-ETHYL-3,4-DIHYDROSPIRO[CHROMENE-2,1-CYCLOBUTAN]-4-YL]AMINO}-1-HYDROXYETHYL]-1,13-DIAZATRICYCLO[13.3.1.1~6,10~]ICOSA-6(20),7,9,15(19),16-PENTAENE-14,18-DIONE'>1R6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=4ke1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ke1 OCA], [https://pdbe.org/4ke1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ke1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ke1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ke1 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 19: | ||
==See Also== | ==See Also== | ||
*[[Beta secretase|Beta secretase]] | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Li | [[Category: Li V]] | ||
[[Category: Long | [[Category: Long AM]] | ||
[[Category: Whittington | [[Category: Whittington DA]] | ||
Latest revision as of 06:08, 21 November 2024
Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 19Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 19
Structural highlights
Publication Abstract from PubMedWe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||