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| | <StructureSection load='2qzk' size='340' side='right'caption='[[2qzk]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='2qzk' size='340' side='right'caption='[[2qzk]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qzk]] is a 1 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=2QZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QZK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qzk]] is a 1 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=2QZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QZK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I21:2-[(5R)-5-AMINO-5-METHYL-4,16-DIOXO-14-PHENYL-3-OXA-15-AZATRICYCLO[15.3.1.1~7,11~]DOCOSA-1(21),7(22),8,10,12,14,17,19-OCTAEN-19-YL]BENZONITRILE'>I21</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qzl|2qzl]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I21:2-[(5R)-5-AMINO-5-METHYL-4,16-DIOXO-14-PHENYL-3-OXA-15-AZATRICYCLO[15.3.1.1~7,11~]DOCOSA-1(21),7(22),8,10,12,14,17,19-OCTAEN-19-YL]BENZONITRILE'>I21</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE ([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=2qzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qzk OCA], [https://pdbe.org/2qzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qzk RCSB], [https://www.ebi.ac.uk/pdbsum/2qzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qzk 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=2qzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qzk OCA], [https://pdbe.org/2qzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qzk RCSB], [https://www.ebi.ac.uk/pdbsum/2qzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qzk 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: Munshi S]] |
| - | [[Category: Munshi, S]] | + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Aspartyl protease]]
| + | |
| - | [[Category: Bace]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[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
This letter describes replacements for the P3 amide moiety present in previously reported tertiary carbinamine macrolactones. Although P-gp efflux issues associated with these amide-macrolactones were solved and full brain penetration was measured in one case, potency was compromised in the process.
Strategies toward improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors.,Moore KP, Zhu H, Rajapakse HA, McGaughey GB, Colussi D, Price EA, Sankaranarayanan S, Simon AJ, Pudvah NT, Hochman JH, Allison T, Munshi SK, Graham SL, Vacca JP, Nantermet PG Bioorg Med Chem Lett. 2007 Nov 1;17(21):5831-5. Epub 2007 Aug 23. PMID:17827011[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
- ↑ Moore KP, Zhu H, Rajapakse HA, McGaughey GB, Colussi D, Price EA, Sankaranarayanan S, Simon AJ, Pudvah NT, Hochman JH, Allison T, Munshi SK, Graham SL, Vacca JP, Nantermet PG. Strategies toward improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5831-5. Epub 2007 Aug 23. PMID:17827011 doi:10.1016/j.bmcl.2007.08.040
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