2iqg

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Hydroxyethyl Secondary Amine-based Peptidomimetic Inhibitor of Human Beta-Secretase (BACE)

Structural highlights

2iqg is a 1 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 1.7Å
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

The design and synthesis of a novel series of potent and cell permeable peptidomimetic inhibitors of the human beta-secretase (BACE) are described. These inhibitors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the C-terminus. The crystal structure of BACE in complex with this hydroxyethyl secondary amine isostere inhibitor is also presented.

Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase.,Maillard MC, Hom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, John V J Med Chem. 2007 Feb 22;50(4):776-81. PMID:17300163^[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
↑ Maillard MC, Hom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, John V. Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase. J Med Chem. 2007 Feb 22;50(4):776-81. PMID:17300163 doi:10.1021/jm061242y

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/2iqg"

@@ Line 1: / Line 1: @@
-[[Image:2iqg.jpg|left|200px]]
-<!--
+==Crystal Structure of Hydroxyethyl Secondary Amine-based Peptidomimetic Inhibitor of Human Beta-Secretase (BACE)==
-The line below this paragraph, containing "STRUCTURE_2iqg", creates the "Structure Box" on the page.
+<StructureSection load='2iqg' size='340' side='right'caption='[[2iqg]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2iqg]] 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=2IQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IQG FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F2I:N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-3-[(3-IODOBENZYL)AMINO]PROPYL}-5-METHYL-N,N-DIPROPYLISOPHTHALAMIDE'>F2I</scene></td></tr>
-{{STRUCTURE_2iqg|  PDB=2iqg  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2iqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iqg OCA], [https://pdbe.org/2iqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iqg RCSB], [https://www.ebi.ac.uk/pdbsum/2iqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iqg 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/iq/2iqg_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=2iqg ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The design and synthesis of a novel series of potent and cell permeable peptidomimetic inhibitors of the human beta-secretase (BACE) are described. These inhibitors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the C-terminus. The crystal structure of BACE in complex with this hydroxyethyl secondary amine isostere inhibitor is also presented.
-'''Crystal Structure of Hydroxyethyl Secondary Amine-based Peptidomimetic Inhibitor of Human Beta-Secretase (BACE)'''
+Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase.,Maillard MC, Hom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, John V J Med Chem. 2007 Feb 22;50(4):776-81. PMID:17300163<ref>PMID:17300163</ref>
-==Overview==
-The design and synthesis of a novel series of potent and cell permeable peptidomimetic inhibitors of the human beta-secretase (BACE) are described. These inhibitors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the C-terminus. The crystal structure of BACE in complex with this hydroxyethyl secondary amine isostere inhibitor is also presented.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-IQG 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=2IQG OCA].
+</div>
+<div class="pdbe-citations 2iqg" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase., Maillard MC, Hom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, John V, J Med Chem. 2007 Feb 22;50(4):776-81. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17300163 17300163]
+*[[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: Benson TE]]
-[[Category: Benson, T E.]]
+[[Category: Emmons TL]]
-[[Category: Emmons, T L.]]
+[[Category: Prince DB]]
-[[Category: Prince, D B.]]
+[[Category: Tomasselli AG]]
-[[Category: Tomasselli, A G.]]
+[[Category: Woods DD]]
-[[Category: Woods, D D.]]
-[[Category: Protein-inhibitor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:46:25 2008''

2iqg

From Proteopedia

Current revision

Crystal Structure of Hydroxyethyl Secondary Amine-based Peptidomimetic Inhibitor of Human Beta-Secretase (BACE)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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