6uj0
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Unbound BACE2 mutant structure== |
| - | <StructureSection load='6uj0' size='340' side='right'caption='[[6uj0]]' scene=''> | + | <StructureSection load='6uj0' size='340' side='right'caption='[[6uj0]], [[Resolution|resolution]] 2.15Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uj0]] 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=6UJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UJ0 FirstGlance]. <br> |
| - | </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=6uj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj0 OCA], [https://pdbe.org/6uj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj0 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj0 ProSAT]</span></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]] 2.15Å</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=6uj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj0 OCA], [https://pdbe.org/6uj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj0 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj0 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6uj0" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Ghosh AK]] |
| + | [[Category: Mesecar AD]] | ||
| + | [[Category: Yen YC]] | ||
Current revision
Unbound BACE2 mutant structure
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