View source for 3zlq


==BACE2 XAPERONE COMPLEX==
<StructureSection load='3zlq' size='340' side='right'caption='[[3zlq]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zlq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZLQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZLQ 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6T9:5-ETHOXY-PYRIDINE-2-CARBOXYLIC+ACID+[3-((R)-2-AMINO-5,5-DIFLUORO-4-METHYL-5,6-DIHYDRO-4H-[1,3]OXAZIN-4-YL)-4-FLUORO-PHENYL]-AMIDE'>6T9</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=3zlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlq OCA], [https://pdbe.org/3zlq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zlq RCSB], [https://www.ebi.ac.uk/pdbsum/3zlq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zlq ProSAT]</span></td></tr>
</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 ==
An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pKa and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF Abeta40 &amp; 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of Abeta40 &amp; 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo.

beta-Secretase (BACE1) Inhibitors with High In Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer's Disease.,Hilpert H, Guba W, Woltering TJ, Wostl W, Pinard E, Mauser H, Mayweg AV, Rogers-Evans M, Humm R, Krummenacher D, Muser T, Schnider C, Jacobsen H, Ozmen L, Bergadano A, Banner DW, Hochstrasser R, Kuglstatter A, David-Pierson P, Fischer H, Polara A, Narquizian R J Med Chem. 2013 Apr 16. PMID:23590342<ref>PMID:23590342</ref>

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

==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Kuglstatter A]]
[[Category: Stihle M]]