View source for 3zks


==BACE2 XAPERONE COMPLEX WITH INHIBITOR==
<StructureSection load='3zks' size='340' side='right'caption='[[3zks]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zks]] is a 2 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=3ZKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZKS 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]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WZV:5-(2,2,2-TRIFLUORO-ETHOXY)-PYRIDINE-2-CARBOXYLIC+ACID+[3-((S)-2-AMINO-1,4-DIMETHYL-6-OXO-1,4,5,6-TETRAHYDRO-PYRIMIDIN-4-YL)-PHENYL]-AMIDE'>WZV</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=3zks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zks OCA], [https://pdbe.org/3zks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zks RCSB], [https://www.ebi.ac.uk/pdbsum/3zks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zks 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 ==
The aspartic protease BACE2 is responsible for the shedding of the transmembrane protein Tmem27 from the surface of pancreatic beta-cells, which leads to inactivation of the beta-cell proliferating activity of Tmem27. This role of BACE2 in the control of beta-cell maintenance suggests BACE2 as a drug target for diabetes. Inhibition of BACE2 has recently been shown to lead to improved control of glucose homeostasis and to increased insulin levels in insulin-resistant mice. BACE2 has 52% sequence identity to the well studied Alzheimer's disease target enzyme beta-secretase (BACE1). High-resolution BACE2 structures would contribute significantly to the investigation of this enzyme as either a drug target or anti-target. Surface mutagenesis, BACE2-binding antibody Fab fragments, single-domain camelid antibody VHH fragments (Xaperones) and Fyn-kinase-derived SH3 domains (Fynomers) were used as crystallization helpers to obtain the first high-resolution structures of BACE2. Eight crystal structures in six different packing environments define an ensemble of low-energy conformations available to the enzyme. Here, the different strategies used for raising and selecting BACE2 binders for cocrystallization are described and the crystallization success, crystal quality and the time and resources needed to obtain suitable crystals are compared.

Mapping the conformational space accessible to BACE2 using surface mutants and cocrystals with Fab fragments, Fynomers and Xaperones.,Banner DW, Gsell B, Benz J, Bertschinger J, Burger D, Brack S, Cuppuleri S, Debulpaep M, Gast A, Grabulovski D, Hennig M, Hilpert H, Huber W, Kuglstatter A, Kusznir E, Laeremans T, Matile H, Miscenic C, Rufer AC, Schlatter D, Steyaert J, Stihle M, Thoma R, Weber M, Ruf A Acta Crystallogr D Biol Crystallogr. 2013 Jun;69(Pt 6):1124-37. doi:, 10.1107/S0907444913006574. Epub 2013 May 15. PMID:23695257<ref>PMID:23695257</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zks" 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: Banner DW]]
[[Category: Benz J]]
[[Category: Kuglstatter A]]
[[Category: Ruf A]]
[[Category: Stihle M]]