2qk5: Difference between revisions

Latest revision as of 05:28, 17 October 2024

Structure of BACE1 bound to SCH626485

Structural highlights

2qk5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:	CS5
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.,Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:18023580^[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
↑ Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:18023580 doi:10.1016/j.bmcl.2007.10.116

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:18023580 doi:10.1016/j.bmcl.2007.10.116

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-[[Image:2qk5.jpg|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2qk5", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_2qk5|  PDB=2qk5  |  SCENE=  }}
-'''Structure of BACE1 bound to SCH626485'''
+==Structure of BACE1 bound to SCH626485==
+<StructureSection load='2qk5' size='340' side='right'caption='[[2qk5]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2qk5]] is a 2 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=2QK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QK5 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CS5:N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-5-METHYL-N,N-DIPROPYLISOPHTHALAMIDE'>CS5</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=2qk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qk5 OCA], [https://pdbe.org/2qk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qk5 RCSB], [https://www.ebi.ac.uk/pdbsum/2qk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qk5 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qk/2qk5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qk5 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.
-==Overview==
+Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.,Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:18023580<ref>PMID:18023580</ref>
-Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-QK5 is a [[Single protein]] structure of 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=2QK5 OCA].
+</div>
+<div class="pdbe-citations 2qk5" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Potent pyrrolidine- and piperidine-based BACE-1 inhibitors., Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J, Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18023580 18023580]
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Iserloh U]]
-[[Category: Iserloh, U.]]
+[[Category: Strickland CO]]
-[[Category: Strickland, C O.]]
-[[Category: Alternative splicing]]
-[[Category: Aspartyl protease]]
-[[Category: Bace1]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Protease]]
-[[Category: Transmembrane]]
-[[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 15:06:13 2008''

2qk5: Difference between revisions

Latest revision as of 05:28, 17 October 2024

Structure of BACE1 bound to SCH626485

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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