3ufl

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:45, 30 October 2024) (edit) (undo)
 
(4 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3ufl.jpg|left|200px]]
 
-
<!--
+
==Discovery of Pyrrolidine-based b-Secretase Inhibitors: Lead Advancement through Conformational Design for Maintenance of Ligand Binding Efficiency==
-
The line below this paragraph, containing "STRUCTURE_3ufl", creates the "Structure Box" on the page.
+
<StructureSection load='3ufl' size='340' side='right'caption='[[3ufl]], [[Resolution|resolution]] 1.90&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'>[[3ufl]] 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=3UFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UFL 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]] 1.9&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=508:(1R,4S)-3,4-DIHYDRO-2H-SPIRO[NAPHTHALENE-1,3-PYRROLIDIN]-4-YL[(2S,4R)-2,4-DIPHENYLPIPERIDIN-1-YL]METHANONE'>508</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
{{STRUCTURE_3ufl| PDB=3ufl | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ufl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufl OCA], [https://pdbe.org/3ufl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ufl RCSB], [https://www.ebi.ac.uk/pdbsum/3ufl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ufl 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 ==
 +
We have developed a novel series of pyrrolidine derived BACE-1 inhibitors. The potency of the weak initial lead structure was enhanced using library-based SAR methods. The series was then further advanced by rational design while maintaining a minimal ligand binding efficiency threshold. Ultimately, the co-crystal structure was obtained revealing that these inhibitors interacted with the enzyme in a unique fashion. In all, the potency of the series was enhanced by 4 orders of magnitude from the HTS lead with concomitant increases in physical properties needed for series advancement. The progression of these developments in a systematic fashion is described.
-
===Discovery of Pyrrolidine-based b-Secretase Inhibitors: Lead Advancement through Conformational Design for Maintenance of Ligand Binding Efficiency===
+
Discovery of pyrrolidine-based beta-secretase inhibitors: Lead advancement through conformational design for maintenance of ligand binding efficiency.,Stachel SJ, Steele TG, Petrocchi A, Haugabook SJ, McGaughey G, Katharine Holloway M, Allison T, Munshi S, Zuck P, Colussi D, Tugasheva K, Wolfe A, Graham SL, Vacca JP Bioorg Med Chem Lett. 2012 Jan 1;22(1):240-4. Epub 2011 Nov 12. PMID:22130130<ref>PMID:22130130</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3ufl" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_22130130}}, adds the Publication Abstract to the page
+
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 22130130 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_22130130}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
[[3ufl]] 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=3UFL OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:022130130</ref><references group="xtra"/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Memapsin 2]]
+
[[Category: Large Structures]]
-
[[Category: Allison, T.]]
+
[[Category: Allison T]]
-
[[Category: Munshi, S.]]
+
[[Category: Munshi S]]
-
[[Category: Soisson, S M.]]
+
[[Category: Soisson SM]]
-
[[Category: Aspartyl protease]]
+
-
[[Category: Hydrolase-hydrolase inhibitor complex]]
+

Current revision

Discovery of Pyrrolidine-based b-Secretase Inhibitors: Lead Advancement through Conformational Design for Maintenance of Ligand Binding Efficiency

PDB ID 3ufl

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/3ufl"
Personal tools