6fgy
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Human BACE-1 in Complex with amino-1,4-oxazine compound 4== | |
| + | <StructureSection load='6fgy' size='340' side='right' caption='[[6fgy]], [[Resolution|resolution]] 1.54Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6fgy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FGY FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D9W:~{N}-[3-[(3~{R})-5-azanyl-3-methyl-2,6-dihydro-1,4-oxazin-3-yl]phenyl]-5-bromanyl-pyridine-2-carboxamide'>D9W</scene></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=6fgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgy OCA], [http://pdbe.org/6fgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fgy RCSB], [http://www.ebi.ac.uk/pdbsum/6fgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgy ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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 == | ||
| + | New amino-1,4-oxazine derived BACE-1 inhibitors were explored and various synthetic routes developed. The binding mode of the inhibitors was elucidated by co-crystallization of 4 with BACE-1 and X-ray analysis. Subsequent optimization led to inhibitors with low double digit nanomolar activity in a biochemical and single digit nanomolar potency in a cellular assays. To assess the inhibitors for their permeation properties and potential to cross the blood-brain-barrier a MDR1-MDCK cell model was successfully applied. Compound 8a confirmed the in vitro results by dose-dependently reducing Abeta levels in mice in an acute treatment regimen. | ||
| - | + | Discovery of amino-1,4-oxazines as potent BACE-1 inhibitors.,Veenstra SJ, Rueeger H, Voegtle M, Lueoend R, Holzer P, Hurth K, Tintelnot-Blomley M, Frederiksen M, Rondeau JM, Jacobson L, Staufenbiel M, Neumann U, Machauer R Bioorg Med Chem Lett. 2018 May 3. pii: S0960-894X(18)30393-7. doi:, 10.1016/j.bmcl.2018.05.003. PMID:29764741<ref>PMID:29764741</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6fgy" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Memapsin 2]] | ||
[[Category: Bourgier, E]] | [[Category: Bourgier, E]] | ||
| - | [[Category: Rondeau, J | + | [[Category: Rondeau, J M]] |
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Oxazine]] | ||
Revision as of 06:01, 6 June 2018
Crystal Structure of Human BACE-1 in Complex with amino-1,4-oxazine compound 4
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