4dh6: Difference between revisions

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-{{STRUCTURE_4dh6|  PDB=4dh6  |  SCENE=  }}
-===Structure of Bace-1 (Beta-Secretase) in Complex with (2R)-N-((2S,3R)-1-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-((S)-6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridine]-4'-ylamino)butan-2-yl)-2-methoxypropanamide===
-{{ABSTRACT_PUBMED_22468639}}
-==Function==
+==Structure of Bace-1 (Beta-Secretase) in Complex with (2R)-N-((2S,3R)-1-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-((S)-6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridine]-4'-ylamino)butan-2-yl)-2-methoxypropanamide==
-[[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>
+<StructureSection load='4dh6' size='340' side='right'caption='[[4dh6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4dh6]] 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=4DH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DH6 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]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0KN:(2R)-N-[(2S,3R)-1-(1,3-BENZODIOXOL-5-YL)-4-{[(4S)-6-(2,2-DIMETHYLPROPYL)-3,4-DIHYDROSPIRO[CYCLOBUTANE-1,2-PYRANO[2,3-B]PYRIDIN]-4-YL]AMINO}-3-HYDROXYBUTAN-2-YL]-2-METHOXYPROPANAMIDE'>0KN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=4dh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dh6 OCA], [https://pdbe.org/4dh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dh6 RCSB], [https://www.ebi.ac.uk/pdbsum/4dh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dh6 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 series of potent hydroxyethyl amine (HEA) derived inhibitors of ss-site APP cleaving enzyme (BACE) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogs that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS ss-amyloid (Ass) in Sprague Dawley rats following oral administration.
-==About this Structure==
+Design and preparation of a potent series of hydroxyethylamine containing beta-secretase inhibitors that demonstrate robust reduction of central ss-amyloid.,Weiss MM, Williamson T, Babu-Khan S, Bartberger MD, Brown J, Chen K, Cheng Y, Citron M, Croghan MD, Dineen TA, Esmay J, Graceffa RF, Harried S, Hickman D, Hitchcock SA, Horne DB, Huang H, Imbeah-Ampiah R, Judd T, Kaller MR, Kreiman CR, La DS, Li V, Lopez P, Louie S, Monenschein H, Nguyen TT, Pennington LD, Rattan C, San Miguel T, Sickmier EA, Wahl RC, Wen PH, Wood S, Xue Q, Yang BH, Patel VF, Zhong W J Med Chem. 2012 Apr 2. PMID:22468639<ref>PMID:22468639</ref>
-[[4dh6]] is a 1 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=4DH6 OCA].
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4dh6" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Beta secretase|Beta secretase]]
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:022468639</ref><references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Sickmier, E A.]]
+[[Category: Sickmier EA]]
-[[Category: Aspartyl protease]]
-[[Category: Bace-1]]
-[[Category: Beta-secretase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]