3wb4: Difference between revisions

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-{{STRUCTURE_3wb4|  PDB=3wb4  |  SCENE=  }}
-===Crystal Structure of beta secetase in complex with 2-amino-3,6-dimethyl-6-(2-phenylethyl)-3,4,5,6-tetrahydropyrimidin-4-one===
-{{ABSTRACT_PUBMED_24051074}}
-==Function==
+==Crystal Structure of beta secetase in complex with 2-amino-3,6-dimethyl-6-(2-phenylethyl)-3,4,5,6-tetrahydropyrimidin-4-one==
-[[http://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>
+<StructureSection load='3wb4' size='340' side='right'caption='[[3wb4]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3wb4]] 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=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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</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='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>
+<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.
-==About this Structure==
+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>
-[[3wb4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WB4 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:024051074</ref><references group="xtra"/><references/>
+</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: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Arisawa, M.]]
+[[Category: Arisawa M]]
-[[Category: Fujiwara, K.]]
+[[Category: Fujiwara K]]
-[[Category: Hattori, K.]]
+[[Category: Hattori K]]
-[[Category: Hosono, M.]]
+[[Category: Hosono M]]
-[[Category: Muto, C.]]
+[[Category: Muto C]]
-[[Category: Nakano, T.]]
+[[Category: Nakano T]]
-[[Category: Shuto, S.]]
+[[Category: Shuto S]]
-[[Category: Takemoto, H.]]
+[[Category: Takemoto H]]
-[[Category: Tanaka, Y.]]
+[[Category: Tanaka Y]]
-[[Category: Yamakawa, H.]]
+[[Category: Yamakawa H]]
-[[Category: Yamamoto, T.]]
+[[Category: Yamamoto T]]
-[[Category: Yonezawa, S.]]
+[[Category: Yonezawa S]]
-[[Category: Asp2]]
-[[Category: Hydrolase]]
-[[Category: Memapsin-2]]
-[[Category: Membrane-associated aspartic protease 2]]
-[[Category: Protease 2]]