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<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6uj1]] 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=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UJ1 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UJ1 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]] 3.03&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.03&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L3M:(3S)-3-hydroxy-N-(2-methylpropyl)-N~2~-{[(4S)-17-[(methylsulfonyl)(propyl)amino]-2-oxo-3-azatricyclo[13.3.1.1~6,10~]icosa-1(19),6(20),7,9,15,17-hexaen-4-yl]methyl}-L-norleucinamide'>L3M</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L3M:(3S)-3-hydroxy-N-(2-methylpropyl)-N~2~-{[(4S)-17-[(methylsulfonyl)(propyl)amino]-2-oxo-3-azatricyclo[13.3.1.1~6,10~]icosa-1(19),6(20),7,9,15,17-hexaen-4-yl]methyl}-L-norleucinamide'>L3M</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=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [https://pdbe.org/6uj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></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=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [https://pdbe.org/6uj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BACE2_HUMAN BACE2_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading 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. It has also been shown that it can cleave APP between residues 671 and 672.<ref>PMID:10591213</ref> <ref>PMID:11083922</ref> <ref>PMID:15857888</ref> <ref>PMID:11423558</ref> <ref>PMID:16816112</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ability to perform routine structure-guided drug design for selective BACE inhibitors has been limited because of the lack of robust platform for BACE2 expression, purification, and crystallization. To overcome this limitation, we developed a platform that produces 2-3 mg of pure BACE2 protein per liter of E. coli culture, and we used this protein to design macrocyclic compounds that potently and selectively inhibit BACE1 over BACE2. Compound 2 was found to potently inhibit BACE 1 (Ki = 5 nM) with a selectivity of 214-fold over BACE2. The X-ray crystal structures of unbound BACE2 (2.2 A) and BACE2 bound to compound 3 (3.0 A and Ki = 7 nM) were determined and compared to the X-ray structures of BACE1 revealing the S1-S3 subsite as a selectivity determinant. This platform should enable a more rapid development of new and selective BACE inhibitors for the treatment of Alzheimer's disease or type II diabetes.
A Structure-Based Discovery Platform for BACE2 and the Development of Selective BACE Inhibitors.,Yen YC, Kammeyer AM, Tirlangi J, Ghosh AK, Mesecar AD ACS Chem Neurosci. 2021 Feb 17;12(4):581-588. doi: 10.1021/acschemneuro.0c00629. , Epub 2021 Feb 5. PMID:33544569<ref>PMID:33544569</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6uj1" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Ghosh AK]]
[[Category: Ghosh AK]]
[[Category: Mesecar AD]]
[[Category: Mesecar AD]]
[[Category: Yen YC]]
[[Category: Yen YC]]

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