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| | <StructureSection load='5qcu' size='340' side='right'caption='[[5qcu]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='5qcu' size='340' side='right'caption='[[5qcu]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5qcu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QCU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5QCU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5qcu]] is a 3 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=5QCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QCU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E51:(2R,4S)-N-butyl-4-[(5S,8S,10R)-5,10-dimethyl-3,3,6-trioxo-3lambda~6~-thia-7-azabicyclo[11.3.1]heptadeca-1(17),13,15-trien-8-yl]-4-hydroxy-2-methylbutanamide'>E51</scene></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]] 1.951Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E51:(2R,4S)-N-butyl-4-[(5S,8S,10R)-5,10-dimethyl-3,3,6-trioxo-3lambda~6~-thia-7-azabicyclo[11.3.1]heptadeca-1(17),13,15-trien-8-yl]-4-hydroxy-2-methylbutanamide'>E51</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </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=5qcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qcu OCA], [https://pdbe.org/5qcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qcu RCSB], [https://www.ebi.ac.uk/pdbsum/5qcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qcu ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5qcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qcu OCA], [http://pdbe.org/5qcu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qcu RCSB], [http://www.ebi.ac.uk/pdbsum/5qcu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qcu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Memapsin 2]]
| + | [[Category: Burley SK]] |
| - | [[Category: Burley, S K]] | + | [[Category: Rondeau JM]] |
| - | [[Category: Rondeau, J M]] | + | [[Category: Shao C]] |
| - | [[Category: Shao, C]] | + | [[Category: Yang H]] |
| - | [[Category: Yang, H]] | + | |
| - | [[Category: Bace]]
| + | |
| - | [[Category: D3r]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydroloase]]
| + | |
| - | [[Category: Ligand docking]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
The Drug Design Data Resource (D3R) aims to identify best practice methods for computer aided drug design through blinded ligand pose prediction and affinity challenges. Herein, we report on the results of Grand Challenge 4 (GC4). GC4 focused on proteins beta secretase 1 and Cathepsin S, and was run in an analogous manner to prior challenges. In Stage 1, participant ability to predict the pose and affinity of BACE1 ligands were assessed. Following the completion of Stage 1, all BACE1 co-crystal structures were released, and Stage 2 tested affinity rankings with co-crystal structures. We provide an analysis of the results and discuss insights into determined best practice methods.
D3R grand challenge 4: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies.,Parks CD, Gaieb Z, Chiu M, Yang H, Shao C, Walters WP, Jansen JM, McGaughey G, Lewis RA, Bembenek SD, Ameriks MK, Mirzadegan T, Burley SK, Amaro RE, Gilson MK J Comput Aided Mol Des. 2020 Feb;34(2):99-119. doi: 10.1007/s10822-020-00289-y., Epub 2020 Jan 23. PMID:31974851[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
- ↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
- ↑ Parks CD, Gaieb Z, Chiu M, Yang H, Shao C, Walters WP, Jansen JM, McGaughey G, Lewis RA, Bembenek SD, Ameriks MK, Mirzadegan T, Burley SK, Amaro RE, Gilson MK. D3R grand challenge 4: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies. J Comput Aided Mol Des. 2020 Feb;34(2):99-119. doi: 10.1007/s10822-020-00289-y., Epub 2020 Jan 23. PMID:31974851 doi:http://dx.doi.org/10.1007/s10822-020-00289-y
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