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3qi1

From Proteopedia

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Current revision

Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors: prime side chromane-containing inhibitors

Structural highlights

3qi1 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:
Gene:	BACE, BACE1, 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

The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar substituents provided improvements in the compound's in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane.

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors.,Ng RA, Sun M, Bowers S, Hom RK, Probst GD, John V, Fang LY, Maillard M, Gailunas A, Brogley L, Neitz RJ, Tung JS, Pleiss MA, Konradi AW, Sham HL, Dappen MS, Adler M, Yao N, Zmolek W, Nakamura D, Quinn KP, Sauer JM, Bova MP, Ruslim L, Artis DR, Yednock TA Bioorg Med Chem Lett. 2013 Aug 15;23(16):4674-9. doi: 10.1016/j.bmcl.2013.06.006., Epub 2013 Jun 11. PMID:23856050^[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
↑ Ng RA, Sun M, Bowers S, Hom RK, Probst GD, John V, Fang LY, Maillard M, Gailunas A, Brogley L, Neitz RJ, Tung JS, Pleiss MA, Konradi AW, Sham HL, Dappen MS, Adler M, Yao N, Zmolek W, Nakamura D, Quinn KP, Sauer JM, Bova MP, Ruslim L, Artis DR, Yednock TA. Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors. Bioorg Med Chem Lett. 2013 Aug 15;23(16):4674-9. doi: 10.1016/j.bmcl.2013.06.006., Epub 2013 Jun 11. PMID:23856050 doi:http://dx.doi.org/10.1016/j.bmcl.2013.06.006

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/3qi1"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 3qi1 is ON HOLD
+==Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors: prime side chromane-containing inhibitors==
+<StructureSection load='3qi1' size='340' side='right'caption='[[3qi1]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3qi1]] 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=3QI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QI1 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C6A:N-[(2S,3R)-4-{[(2R,4S)-2-CYCLOPROPYL-6-(2,2-DIMETHYLPROPYL)-3,4-DIHYDRO-2H-CHROMEN-4-YL]AMINO}-1-(3,5-DIFLUOROPHENYL)-3-HYDROXYBUTAN-2-YL]ACETAMIDE'>C6A</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE, BACE1, 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=3qi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qi1 OCA], [https://pdbe.org/3qi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qi1 RCSB], [https://www.ebi.ac.uk/pdbsum/3qi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qi1 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 ==
+The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar substituents provided improvements in the compound's in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane.
-Authors: Yao, N.
+Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors.,Ng RA, Sun M, Bowers S, Hom RK, Probst GD, John V, Fang LY, Maillard M, Gailunas A, Brogley L, Neitz RJ, Tung JS, Pleiss MA, Konradi AW, Sham HL, Dappen MS, Adler M, Yao N, Zmolek W, Nakamura D, Quinn KP, Sauer JM, Bova MP, Ruslim L, Artis DR, Yednock TA Bioorg Med Chem Lett. 2013 Aug 15;23(16):4674-9. doi: 10.1016/j.bmcl.2013.06.006., Epub 2013 Jun 11. PMID:23856050<ref>PMID:23856050</ref>
-Description: Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Prime side chromane-containing inhibitors
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3qi1" 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: Yao, N]]
+[[Category: Aspartate protease]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]

3qi1

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Current revision

Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors: prime side chromane-containing inhibitors

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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