3u6a
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 3u6a is ON HOLD Authors: Spurlino, J.C., Alexander, R.A. Description: Rational Design and Synthesis of Aminopiperazinones as Beta Secretase (BACE) ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Rational Design and Synthesis of Aminopiperazinones as Beta Secretase (BACE) Inhibitors== | |
| + | <StructureSection load='3u6a' size='340' side='right'caption='[[3u6a]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3u6a]] 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=3U6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U6A 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]] 2.199Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=18P:N-{3-[(2R)-6-AMINO-2,4-DIMETHYL-3-OXO-2,3,4,5-TETRAHYDROPYRAZIN-2-YL]PHENYL}-5-CHLOROPYRIDINE-2-CARBOXAMIDE'>18P</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=3u6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u6a OCA], [https://pdbe.org/3u6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u6a RCSB], [https://www.ebi.ac.uk/pdbsum/3u6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u6a ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor, (-)-37, which showed in vivo reduction of amyloid beta peptides. The crystal structure of 18a showed a binding mode driven by interaction with the catalytic aspartate dyad and distribution of the biaryl amide decoration towards S1 and S3 pockets. | ||
| - | + | Rational design and synthesis of aminopiperazinones as beta-secretase (BACE) inhibitors.,Tresadern G, Delgado F, Delgado O, Gijsen H, Macdonald GJ, Moechars D, Rombouts F, Alexander R, Spurlino J, Van Gool M, Vega JA, Trabanco AA Bioorg Med Chem Lett. 2011 Dec 15;21(24):7255-60. doi:, 10.1016/j.bmcl.2011.10.050. Epub 2011 Oct 20. PMID:22071305<ref>PMID:22071305</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3u6a" 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: Alexander RS]] | ||
| + | [[Category: Spurlino JC]] | ||
Current revision
Rational Design and Synthesis of Aminopiperazinones as Beta Secretase (BACE) Inhibitors
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