View source for 3skg


==Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with (2S)-2-((3R)-3-acetamido-3-isobutyl-2-oxo-1-pyrrolidinyl)-N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-2-(1,2,3,4-tetrahydro-3-isoquinolinyl)ethyl)-4-phenylbutanamide==
<StructureSection load='3skg' size='340' side='right'caption='[[3skg]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3skg]] is a 4 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=3SKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SKG 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]] 2.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PB8:(2S)-2-[(3R)-3-(ACETYLAMINO)-3-(2-METHYLPROPYL)-2-OXOPYRROLIDIN-1-YL]-N-{(1R,2S)-3-(3,5-DIFLUOROPHENYL)-1-HYDROXY-1-[(3R)-1,2,3,4-TETRAHYDROISOQUINOLIN-3-YL]PROPAN-2-YL}-4-PHENYLBUTANAMIDE'>PB8</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=3skg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3skg OCA], [https://pdbe.org/3skg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3skg RCSB], [https://www.ebi.ac.uk/pdbsum/3skg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3skg 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> 
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== Publication Abstract from PubMed ==
The synthesis, evaluation, and structure-activity relationships of a set of related constrained diaminopropane inhibitors of BACE-1 are described. The full in vivo profile of an optimized inhibitor in both normal and P-gp deficient mice is compared with data generated in normal rats.

Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors.,Thompson LA, Shi J, Decicco CP, Tebben AJ, Olson RE, Boy KM, Guernon JM, Good AC, Liauw A, Zheng C, Copeland RA, Combs AP, Trainor GL, Camac DM, Muckelbauer JK, Lentz KA, Grace JE, Burton CR, Toyn JH, Barten DM, Marcinkeviciene J, Meredith JE, Albright CF, Macor JE Bioorg Med Chem Lett. 2011 Nov 15;21(22):6909-15. Epub 2011 Jul 2. PMID:21974952<ref>PMID:21974952</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3skg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Muckelbauer JK]]