3ohf

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[[Image:3ohf.jpg|left|200px]]
 
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==Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with bms-655295 aka n~3~-((1s,2r)-1- benzyl-2-hydroxy-3-((3-methoxybenzyl)amino)propyl)-n~1~, n~1~-dibutyl-1h-indole-1,3-dicarboxamide==
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The line below this paragraph, containing "STRUCTURE_3ohf", creates the "Structure Box" on the page.
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<StructureSection load='3ohf' size='340' side='right'caption='[[3ohf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3ohf]] is a 2 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=3OHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OHF 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]] 2.1&#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=3HF:N~3~-{(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-N~1~,N~1~-DIBUTYL-1H-INDOLE-1,3-DICARBOXAMIDE'>3HF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
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{{STRUCTURE_3ohf| PDB=3ohf | SCENE= }}
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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=3ohf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ohf OCA], [https://pdbe.org/3ohf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ohf RCSB], [https://www.ebi.ac.uk/pdbsum/3ohf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ohf 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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Heterocyclic replacement of the isophthalamide phenyl ring in hydroxyethylamine (HEA) BACE-1 inhibitors was explored. A variety of indole-1,3-dicarboxamide HEAs exhibited potent BACE-1 enzyme inhibition, but displayed poor cellular activity. Improvements in cellular activity and aspartic protease selectivity were observed for 7-azaindole-1,3-dicarboxamide HEAs. A methylprolinol-bearing derivative (10n) demonstrated robust reductions in rat plasma Abeta levels, but did not lower rat brain Abeta due to poor central exposure. The same analog exhibited a high efflux ratio in a bidirectional Caco-2 assay and was likely a substrate of the efflux transporter P-glycoprotein. X-ray crystal structures are reported for two indole HEAs in complex with BACE-1.
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===Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with bms-655295 aka n~3~-((1s,2r)-1- benzyl-2-hydroxy-3-((3-methoxybenzyl)amino)propyl)-n~1~, n~1~-dibutyl-1h-indole-1,3-dicarboxamide===
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Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1.,Marcin LR, Higgins MA, Zusi FC, Zhang Y, Dee MF, Parker MF, Muckelbauer JK, Camac DM, Morin PE, Ramamurthy V, Tebben AJ, Lentz KA, Grace JE, Marcinkeviciene JA, Kopcho LM, Burton CR, Barten DM, Toyn JH, Meredith JE, Albright CF, Bronson JJ, Macor JE, Thompson LA Bioorg Med Chem Lett. 2011 Jan 1;21(1):537-41. PMID:21078556<ref>PMID:21078556</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 3ohf" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_21078556}}, adds the Publication Abstract to the page
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 21078556 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_21078556}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3ohf]] is a 2 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=3OHF OCA].
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==Reference==
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<ref group="xtra">PMID:21078556</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Memapsin 2]]
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[[Category: Large Structures]]
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[[Category: Muckelbauer, J K.]]
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[[Category: Muckelbauer JK]]

Current revision

Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with bms-655295 aka n~3~-((1s,2r)-1- benzyl-2-hydroxy-3-((3-methoxybenzyl)amino)propyl)-n~1~, n~1~-dibutyl-1h-indole-1,3-dicarboxamide

PDB ID 3ohf

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