4dus

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[[Image:4dus.jpg|left|200px]]
 
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{{STRUCTURE_4dus| PDB=4dus | SCENE= }}
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==Structure of Bace-1 (Beta-Secretase) in complex with N-((2S,3R)-1-(4-fluorophenyl)-3-hydroxy-4-((6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl)amino)butan-2-yl)acetamide==
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<StructureSection load='4dus' size='340' side='right'caption='[[4dus]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4dus]] 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=4DUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DUS FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MP:N-((2S,3R)-1-(4-FLUOROPHENYL)-3-HYDROXY-4-((6-NEOPENTYL-3,4-DIHYDROSPIRO[CYCLOBUTANE-1,2-PYRANO[2,3-B]PYRIDIN]-4-YL)AMINO)BUTAN-2-YL)ACETAMIDE'>0MP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dus OCA], [https://pdbe.org/4dus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dus RCSB], [https://www.ebi.ac.uk/pdbsum/4dus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dus ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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beta-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against beta-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Abeta40 levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor.
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===Structure of Bace-1 (Beta-Secretase) in complex with N-((2S,3R)-1-(4-fluorophenyl)-3-hydroxy-4-((6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl)amino)butan-2-yl)acetamide===
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A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of beta-Secretase.,Kaller MR, Harried SS, Albrecht B, Amarante P, Babu-Khan S, Bartberger MD, Brown J, Brown R, Chen K, Cheng Y, Citron M, Croghan MD, Graceffa R, Hickman D, Judd T, Kriemen C, La D, Li V, Lopez P, Luo Y, Masse C, Monenschein H, Nguyen T, Pennington LD, Miguel TS, Sickmier EA, Wahl RC, Weiss MM, Wen PH, Williamson T, Wood S, Xue M, Yang B, Zhang J, Patel V, Zhong W, Hitchcock S ACS Med Chem Lett. 2012 Mar 29;3(11):886-91. doi: 10.1021/ml3000148. eCollection , 2012 Nov 8. PMID:24900403<ref>PMID:24900403</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4dus" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[4dus]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DUS OCA].
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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[[Category: Memapsin 2]]
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== References ==
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[[Category: Sickmier, E A.]]
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<references/>
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[[Category: App]]
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__TOC__
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[[Category: Aspartyl protease]]
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</StructureSection>
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[[Category: Hydrolase]]
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[[Category: Homo sapiens]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Large Structures]]
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[[Category: Sickmier EA]]

Current revision

Structure of Bace-1 (Beta-Secretase) in complex with N-((2S,3R)-1-(4-fluorophenyl)-3-hydroxy-4-((6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl)amino)butan-2-yl)acetamide

PDB ID 4dus

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