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| | <StructureSection load='3hw1' size='340' side='right'caption='[[3hw1]], [[Resolution|resolution]] 2.48Å' scene=''> | | <StructureSection load='3hw1' size='340' side='right'caption='[[3hw1]], [[Resolution|resolution]] 2.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hw1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HW1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hw1]] 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=3HW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HW1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EV2:3-PYRROLIDIN-1-YLQUINOXALIN-2-AMINE'>EV2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.48Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3hvg|3hvg]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EV2:3-PYRROLIDIN-1-YLQUINOXALIN-2-AMINE'>EV2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [https://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=3hw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hw1 OCA], [https://pdbe.org/3hw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hw1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hw1 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=3hw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hw1 OCA], [https://pdbe.org/3hw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hw1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hw1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Memapsin 2]]
| + | [[Category: Barker J]] |
| - | [[Category: Barker, J]] | + | [[Category: Ebneth A]] |
| - | [[Category: Ebneth, A]] | + | [[Category: Godemann R]] |
| - | [[Category: Godemann, R]] | + | [[Category: Kramer J]] |
| - | [[Category: Kramer, J]] | + | [[Category: Madden J]] |
| - | [[Category: Madden, J]] | + | [[Category: Smith MA]] |
| - | [[Category: Smith, M A]] | + | |
| - | [[Category: Alzheimer's disease]]
| + | |
| - | [[Category: Amyloid precursor protein secretase]]
| + | |
| - | [[Category: Aspartic endopeptidase]]
| + | |
| - | [[Category: Aspartic protease]]
| + | |
| - | [[Category: Aspartyl protease]]
| + | |
| - | [[Category: Base]]
| + | |
| - | [[Category: Beta-secretase]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Fluorescence polarisation]]
| + | |
| - | [[Category: Fragment-based drug design]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Novel nonpeptidic inhibitors of beta-secretase (BACE1) have been discovered by employing a fragment-based biochemical screening approach. A diverse library of 20000 low-molecular weight compounds were screened and yielded 26 novel hits that were confirmed by biochemical and surface plasmon resonance secondary assays. We describe here fragment inhibitors cocrystallized with BACE1 in a flap open and flap closed conformation as determined by X-ray crystallography.
Fragment-Based Discovery of BACE1 Inhibitors Using Functional Assays.,Godemann R, Madden J, Kramer J, Smith M, Fritz U, Hesterkamp T, Barker J, Hoppner S, Hallett D, Cesura A, Ebneth A, Kemp J Biochemistry. 2009 Oct 23. PMID:19799414[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
- ↑ Godemann R, Madden J, Kramer J, Smith M, Fritz U, Hesterkamp T, Barker J, Hoppner S, Hallett D, Cesura A, Ebneth A, Kemp J. Fragment-Based Discovery of BACE1 Inhibitors Using Functional Assays. Biochemistry. 2009 Oct 23. PMID:19799414 doi:10.1021/bi901061a
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