This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3wb4

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 22:34, 5 August 2016

Crystal Structure of beta secetase in complex with 2-amino-3,6-dimethyl-6-(2-phenylethyl)-3,4,5,6-tetrahydropyrimidin-4-one

Structural highlights

3wb4 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3wb5
Gene:	BACE1, BACE, KIAA1149 (HUMAN)
Activity:	Memapsin 2, with EC number 3.4.23.46
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Yonezawa S, Fujiwara K, Yamamoto T, Hattori K, Yamakawa H, Muto C, Hosono M, Tanaka Y, Nakano T, Takemoto H, Arisawa M, Shuto S. 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. Bioorg Med Chem. 2013 Aug 28. pii: S0968-0896(13)00730-X. doi:, 10.1016/j.bmc.2013.08.036. PMID:24051074 doi:10.1016/j.bmc.2013.08.036

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3wb4"

@@ Line 1: / Line 1: @@
 ==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]] 2.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WB4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3wb4]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WB4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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">[[3wb5|3wb5]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://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'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wb4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wb4 RCSB], [http://www.ebi.ac.uk/pdbsum/3wb4 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wb4 OCA], [http://pdbe.org/3wb4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wb4 RCSB], [http://www.ebi.ac.uk/pdbsum/3wb4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wb4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3wb4" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Memapsin 2]]
 [[Category: Arisawa, M]]

3wb4

From Proteopedia

Revision as of 22:34, 5 August 2016

Crystal Structure of beta secetase in complex with 2-amino-3,6-dimethyl-6-(2-phenylethyl)-3,4,5,6-tetrahydropyrimidin-4-one

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox