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3wb4
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 3wb4 is ON HOLD until Paper Publication Authors: Yonezawa, S., Fujiwara, K., Yamamoto, T., Hattori, K., Yamakawa, H., Muto, C., Hosono, M., Tanaka, ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of beta secetase in complex with 2-amino-3,6-dimethyl-6-(2-phenylethyl)-3,4,5,6-tetrahydropyrimidin-4-one== | |
| + | <StructureSection load='3wb4' size='340' side='right'caption='[[3wb4]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3wb4]] 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=3WB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WB4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0B3:(6R)-2-AMINO-3,6-DIMETHYL-6-(2-PHENYLETHYL)-5,6-DIHYDROPYRIMIDIN-4(3H)-ONE'>0B3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wb5|3wb5]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([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=3wb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wb4 OCA], [https://pdbe.org/3wb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wb4 RCSB], [https://www.ebi.ac.uk/pdbsum/3wb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wb4 ProSAT]</span></td></tr> | ||
| + | </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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | For further investigation of BACE1 inhibitors using conformational restriction with sp3 hybridized carbon, we applied this approach to 6-substituted aminopyrimidone derivatives 3 to improve the inhibitory activity by reducing the entropic energy loss upon binding to BACE1. Among eight stereoisomers synthesized, [trans-(1'R,2'R),6S] isomer 6 exhibited the best BACE1 inhibitory activity, which was statistically superior to that of the corresponding ethylene linker compound (R)-3. Combinational examinations of the binding mode of 6 were performed, which included isothermal titration calorimetry (ITC), X-ray crystallographic structure analysis and theoretical calculations, to clarify the effect of our conformational restriction approach. From the ITC measurement, the binding entropy of 6 was found to be approximately 0.5kcal larger than that of (R)-3, which is considered to be affected by conformational restriction with a cyclopropane ring. | ||
| - | + | Conformational restriction approach to beta-secretase (BACE1) inhibitors III: Effective investigation of the binding mode by combinational use of X-ray analysis, isothermal titration calorimetry and theoretical calculations.,Yonezawa S, Fujiwara K, Yamamoto T, Hattori K, Yamakawa H, Muto C, Hosono M, Tanaka Y, Nakano T, Takemoto H, Arisawa M, Shuto S Bioorg Med Chem. 2013 Aug 28. pii: S0968-0896(13)00730-X. doi:, 10.1016/j.bmc.2013.08.036. PMID:24051074<ref>PMID:24051074</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3wb4" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Memapsin 2]] | ||
| + | [[Category: Arisawa, M]] | ||
| + | [[Category: Fujiwara, K]] | ||
| + | [[Category: Hattori, K]] | ||
| + | [[Category: Hosono, M]] | ||
| + | [[Category: Muto, C]] | ||
| + | [[Category: Nakano, T]] | ||
| + | [[Category: Shuto, S]] | ||
| + | [[Category: Takemoto, H]] | ||
| + | [[Category: Tanaka, Y]] | ||
| + | [[Category: Yamakawa, H]] | ||
| + | [[Category: Yamamoto, T]] | ||
| + | [[Category: Yonezawa, S]] | ||
| + | [[Category: Asp2]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Memapsin-2]] | ||
| + | [[Category: Membrane-associated aspartic protease 2]] | ||
| + | [[Category: Protease 2]] | ||
Current revision
Crystal Structure of beta secetase in complex with 2-amino-3,6-dimethyl-6-(2-phenylethyl)-3,4,5,6-tetrahydropyrimidin-4-one
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Categories: Human | Large Structures | Memapsin 2 | Arisawa, M | Fujiwara, K | Hattori, K | Hosono, M | Muto, C | Nakano, T | Shuto, S | Takemoto, H | Tanaka, Y | Yamakawa, H | Yamamoto, T | Yonezawa, S | Asp2 | Hydrolase | Memapsin-2 | Membrane-associated aspartic protease 2 | Protease 2
