3u6a
From Proteopedia
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| - | + | ==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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U6A FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u6a RCSB], [http://www.ebi.ac.uk/pdbsum/3u6a PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <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> | |
==See Also== | ==See Also== | ||
*[[Beta secretase|Beta secretase]] | *[[Beta secretase|Beta secretase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
| - | [[Category: Alexander, R S | + | [[Category: Alexander, R S]] |
| - | [[Category: Spurlino, J C | + | [[Category: Spurlino, J C]] |
[[Category: Beta-site app cleaving enzyme 1]] | [[Category: Beta-site app cleaving enzyme 1]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 06:46, 21 December 2014
Rational Design and Synthesis of Aminopiperazinones as Beta Secretase (BACE) Inhibitors
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