2qmg

From Proteopedia

(Difference between revisions)

Current revision

Structure of BACE Bound to SCH745966

Structural highlights

2qmg 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 1.89Å
Ligands:	,
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 a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.

Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.,Iserloh U, Pan J, Stamford AW, Kennedy ME, Zhang Q, Zhang L, Parker EM, McHugh NA, Favreau L, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):418-22. Epub 2007 Oct 18. PMID:17980584^[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, Pan J, Stamford AW, Kennedy ME, Zhang Q, Zhang L, Parker EM, McHugh NA, Favreau L, Strickland C, Voigt J. Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor. Bioorg Med Chem Lett. 2008 Jan 1;18(1):418-22. Epub 2007 Oct 18. PMID:17980584 doi:10.1016/j.bmcl.2007.10.053

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qmg"

Categories: Homo sapiens | Large Structures | Iserloh U | Strickland CO

@@ Line 1: / Line 1: @@
-[[Image:2qmg.png|left|200px]]
-{{STRUCTURE_2qmg|  PDB=2qmg  |  SCENE=  }}
+==Structure of BACE Bound to SCH745966==
+<StructureSection load='2qmg' size='340' side='right'caption='[[2qmg]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2qmg]] 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=2QMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QMG 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]] 1.89&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SC6:N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R,4R)-4-PHENOXYPYRROLIDIN-2-YL]ETHYL}-3-{[(2R)-2-(METHOXYMETHYL)PYRROLIDIN-1-YL]CARBONYL}-5-METHYLBENZAMIDE'>SC6</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</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=2qmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qmg OCA], [https://pdbe.org/2qmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qmg RCSB], [https://www.ebi.ac.uk/pdbsum/2qmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qmg 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/qm/2qmg_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=2qmg ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.
-===Structure of BACE Bound to SCH745966===
+Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.,Iserloh U, Pan J, Stamford AW, Kennedy ME, Zhang Q, Zhang L, Parker EM, McHugh NA, Favreau L, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):418-22. Epub 2007 Oct 18. PMID:17980584<ref>PMID:17980584</ref>
-{{ABSTRACT_PUBMED_17980584}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2qmg" style="background-color:#fffaf0;"></div>
-[[2qmg]] is a 2 chain structure of [[Beta secretase]] 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=2QMG OCA].
 ==See Also==
-*[[Beta secretase|Beta secretase]]
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:017980584</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Iserloh, U.]]
+[[Category: Iserloh U]]
-[[Category: Strickland, C O.]]
+[[Category: Strickland CO]]
-[[Category: Aspartyl protease]]
-[[Category: Bace1]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Protease]]
-[[Category: Transmembrane]]
-[[Category: Zymogen]]

2qmg

From Proteopedia

Current revision

Structure of BACE Bound to SCH745966

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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