4zsq: Difference between revisions
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==BACE crystal structure with tricyclic aminothiazine inhibitor== | ==BACE crystal structure with tricyclic aminothiazine inhibitor== | ||
<StructureSection load='4zsq' size='340' side='right' caption='[[4zsq]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='4zsq' size='340' side='right'caption='[[4zsq]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zsq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSQ OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4zsq]] is a 2 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=4ZSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSQ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4RX:N-[(4S,4AS,6S,8AR)-10-AMINOHEXAHYDRO-3H-4,8A-(EPITHIOMETHENOAZENO)ISOCHROMEN-6(1H)-YL]-3-CHLOROBENZAMIDE'>4RX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4RX:N-[(4S,4AS,6S,8AR)-10-AMINOHEXAHYDRO-3H-4,8A-(EPITHIOMETHENOAZENO)ISOCHROMEN-6(1H)-YL]-3-CHLOROBENZAMIDE'>4RX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4zsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsq OCA], [https://pdbe.org/4zsq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsq RCSB], [https://www.ebi.ac.uk/pdbsum/4zsq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsq 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 18: | Line 16: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4zsq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[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: | [[Category: Timm DE]] | ||
Latest revision as of 06:47, 21 November 2024
BACE crystal structure with tricyclic aminothiazine inhibitorBACE crystal structure with tricyclic aminothiazine inhibitor
Structural highlights
Publication Abstract from PubMedThe BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described. Preparation and biological evaluation of conformationally constrained BACE1 inhibitors.,Winneroski LL, Schiffler MA, Erickson JA, May PC, Monk SA, Timm DE, Audia JE, Beck JP, Boggs LN, Borders AR, Boyer RD, Brier RA, Hudziak KJ, Klimkowski VJ, Garcia Losada P, Mathes BM, Stout SL, Watson BM, Mergott DJ Bioorg Med Chem. 2015 Jul 1;23(13):3260-8. doi: 10.1016/j.bmc.2015.04.062. Epub, 2015 May 6. PMID:26001341[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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