4exg
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors== | |
| + | <StructureSection load='4exg' size='340' side='right'caption='[[4exg]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4exg]] 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=4EXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EXG 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=916:N-[(2S,3R)-4-{[(4S)-6-(2,2-DIMETHYLPROPYL)-2,2-DIMETHYL-3,4-DIHYDRO-2H-THIENO[2,3-B]PYRAN-4-YL]AMINO}-3-HYDROXY-1-PHENYLBUTAN-2-YL]ACETAMIDE'>916</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=4exg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4exg OCA], [https://pdbe.org/4exg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4exg RCSB], [https://www.ebi.ac.uk/pdbsum/4exg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4exg 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 == | ||
| + | A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core structure with different prime side alkyl substituted 4,5,6,7-tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized. Striking differences were observed on potencies in the BACE-1 enzymatic and cellular assays depending on the nature of the heteroatoms in the bicyclic ring, from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of 44 nM (enzyme assay) and 65 nM (cell-based assay). | ||
| - | + | Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates.,Sund C, Belda O, Borkakoti N, Lindberg J, Derbyshire D, Vrang L, Hamelink E, Ahgren C, Woestenenk E, Wikstrom K, Eneroth A, Lindstrom E, Kalayanov G Bioorg Med Chem Lett. 2012 Nov 1;22(21):6721-7. doi: 10.1016/j.bmcl.2012.08.097. , Epub 2012 Sep 5. PMID:23010268<ref>PMID:23010268</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4exg" 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: Borkakoti N]] | ||
| + | [[Category: Derbyshire D]] | ||
| + | [[Category: Lindberg J]] | ||
Current revision
Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors
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