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.


4dpi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:33, 21 September 2022) (edit) (undo)
 
(4 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:4dpi.jpg|left|200px]]
 
-
{{STRUCTURE_4dpi| PDB=4dpi | SCENE= }}
+
==BACE-1 in complex with HEA-macrocyclic inhibitor, MV078512==
 +
<StructureSection load='4dpi' size='340' side='right'caption='[[4dpi]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4dpi]] 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=4DPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DPI FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0N1:(4S,8E,11R)-4-[(1R)-1-HYDROXY-2-{[3-(PROPAN-2-YL)BENZYL]AMINO}ETHYL]-16-METHYL-11-PHENYL-6-OXA-3,12-DIAZABICYCLO[12.3.1]OCTADECA-1(18),8,14,16-TETRAENE-2,13-DIONE'>0N1</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=4dpi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpi OCA], [https://pdbe.org/4dpi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dpi RCSB], [https://www.ebi.ac.uk/pdbsum/4dpi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpi 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 ==
 +
A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC(50) values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed.
-
===BACE-1 in complex with HEA-macrocyclic inhibitor, MV078512===
+
Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes.,Sandgren V, Agback T, Johansson PO, Lindberg J, Kvarnstrom I, Samuelsson B, Belda O, Dahlgren A Bioorg Med Chem. 2012 Jul 15;20(14):4377-89. Epub 2012 May 24. PMID:22698785<ref>PMID:22698785</ref>
-
{{ABSTRACT_PUBMED_22698785}}
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 4dpi" style="background-color:#fffaf0;"></div>
-
==About this Structure==
+
==See Also==
-
[[4dpi]] 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=4DPI OCA].
+
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:022698785</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Memapsin 2]]
+
[[Category: Large Structures]]
-
[[Category: Borkakoti, N.]]
+
[[Category: Borkakoti N]]
-
[[Category: Derbyshire, D.]]
+
[[Category: Derbyshire D]]
-
[[Category: Lindberg, J.]]
+
[[Category: Lindberg J]]
-
[[Category: Asp2]]
+
-
[[Category: Bace]]
+
-
[[Category: Bace1]]
+
-
[[Category: Hydrolase-hydrolase inhibitor complex]]
+
-
[[Category: Macrocycle]]
+

Current revision

BACE-1 in complex with HEA-macrocyclic inhibitor, MV078512

PDB ID 4dpi

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dpi"
Personal tools