4fri
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fri]] 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=4FRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FRI FirstGlance]. <br> | <table><tr><td colspan='2'>[[4fri]] 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=4FRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FRI FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DWA:(4R)-4-[3-(2-FLUOROPYRIDIN-3-YL)PHENYL]-4-(4-METHOXYPHENYL)-4,5-DIHYDRO-1,3-OXAZOL-2-AMINE'>DWA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 2.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DWA:(4R)-4-[3-(2-FLUOROPYRIDIN-3-YL)PHENYL]-4-(4-METHOXYPHENYL)-4,5-DIHYDRO-1,3-OXAZOL-2-AMINE'>DWA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></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=4fri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fri OCA], [https://pdbe.org/4fri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fri RCSB], [https://www.ebi.ac.uk/pdbsum/4fri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fri 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=4fri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fri OCA], [https://pdbe.org/4fri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fri RCSB], [https://www.ebi.ac.uk/pdbsum/4fri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fri 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> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human beta-secretase inhibitors. These compounds exhibited good enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound 11a resulted in a robust reduction of CNS Abeta40 in naive rats. | ||
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| - | Structure and Property Based Design of Aminooxazoline Xanthenes as Selective and Orally Efficacious, CNS Penetrable BACE Inhibitors for the Treatment of Alzheimer's Disease.,Huang H, La DS, Cheng AC, Whittington DA, Patel VF, Chen K, Dineen TA, Epstein O, Graceffa R, Hickman D, Kiang YH, Louie S, Luo Y, Wahl R, Wen P, Wood S, Fremeau B J Med Chem. 2012 Aug 28. PMID:22928914<ref>PMID:22928914</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4fri" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Revision as of 15:32, 14 March 2024
Crystal structure of BACE1 in complex with biarylspiro aminooxazoline 6
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