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4n00
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==Discovery of 7-THP chromans: BACE1 inhibitors that reduce A-beta in the CNS== | ==Discovery of 7-THP chromans: BACE1 inhibitors that reduce A-beta in the CNS== | ||
| - | <StructureSection load='4n00' size='340' side='right' caption='[[4n00]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4n00' size='340' side='right'caption='[[4n00]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4n00]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N00 OCA]. <br> | + | <table><tr><td colspan='2'>[[4n00]] 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=4N00 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N00 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2EX:(4R,4AS,10AS)-2-AMINO-8-(2-FLUOROPYRIDIN-3-YL)-1-METHYL-3,4,4A,10A-TETRAHYDRO-1H-SPIRO[IMIDAZOLE-4,10-PYRANO[4,3-B]CHROMEN]-5(1H)-ONE'>2EX</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene> | + | </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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2EX:(4R,4AS,10AS)-2-AMINO-8-(2-FLUOROPYRIDIN-3-YL)-1-METHYL-3,4,4A,10A-TETRAHYDRO-1H-SPIRO[IMIDAZOLE-4,10-PYRANO[4,3-B]CHROMEN]-5(1H)-ONE'>2EX</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | |
| - | <tr | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4n00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n00 OCA], [https://pdbe.org/4n00 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n00 RCSB], [https://www.ebi.ac.uk/pdbsum/4n00 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n00 ProSAT]</span></td></tr> |
| - | + | </table> | |
| - | <table> | + | == 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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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Discovery of 7-tetrahydropyran-2-yl chromans: beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid beta-protein (Abeta) in the central nervous system.,Thomas AA, Hunt KW, Volgraf M, Watts RJ, Liu X, Vigers G, Smith D, Sammond D, Tang TP, Rhodes SP, Metcalf AT, Brown KD, Otten JN, Burkard M, Cox AA, Do MK, Dutcher D, Rana S, DeLisle RK, Regal K, Wright AD, Groneberg R, Scearce-Levie K, Siu M, Purkey HE, Lyssikatos JP, Gunawardana IW J Med Chem. 2014 Feb 13;57(3):878-902. doi: 10.1021/jm401635n. Epub 2014 Jan 22. PMID:24397738<ref>PMID:24397738</ref> | Discovery of 7-tetrahydropyran-2-yl chromans: beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid beta-protein (Abeta) in the central nervous system.,Thomas AA, Hunt KW, Volgraf M, Watts RJ, Liu X, Vigers G, Smith D, Sammond D, Tang TP, Rhodes SP, Metcalf AT, Brown KD, Otten JN, Burkard M, Cox AA, Do MK, Dutcher D, Rana S, DeLisle RK, Regal K, Wright AD, Groneberg R, Scearce-Levie K, Siu M, Purkey HE, Lyssikatos JP, Gunawardana IW J Med Chem. 2014 Feb 13;57(3):878-902. doi: 10.1021/jm401635n. Epub 2014 Jan 22. PMID:24397738<ref>PMID:24397738</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
</div> | </div> | ||
| + | <div class="pdbe-citations 4n00" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Smith D]] |
| - | [[Category: | + | [[Category: Vigers GPA]] |
| - | + | ||
Current revision
Discovery of 7-THP chromans: BACE1 inhibitors that reduce A-beta in the CNS
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