3igb

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:00, 9 October 2024) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3igb.png|left|200px]]
 
-
<!--
+
==Bace-1 with Compound 3==
-
The line below this paragraph, containing "STRUCTURE_3igb", creates the "Structure Box" on the page.
+
<StructureSection load='3igb' size='340' side='right'caption='[[3igb]], [[Resolution|resolution]] 2.24&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'>[[3igb]] 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=3IGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IGB 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]] 2.238&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=454:8,8-DIPHENYL-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>454</scene></td></tr>
-
{{STRUCTURE_3igb| PDB=3igb | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3igb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3igb OCA], [https://pdbe.org/3igb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3igb RCSB], [https://www.ebi.ac.uk/pdbsum/3igb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3igb 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/ig/3igb_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=3igb ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The identification of small molecule aminoimidazoles as potent and selective human beta-secretase inhibitors is reported. These analogues demonstrate low nannomolar potency for BACE1 in a FRET assay, exhibit comparable activity in a cell-based (ELISA) assay, and show &gt;100x selectivity for the other structurally related aspartyl proteases BACE2, cathepsin D, renin, and pepsin. Our design strategy was supported by molecular modeling studies based on the cocrystal structure of the HTS-hit 3 in the BACE1 active site. These strategies enabled us to integrate pyridine and pyrimidine groups on 3 extending deep into the S3 region of the BACE1 binding pocket and enhancing the ligand's potency. Compound (R)-37 displayed an IC50 value for BACE1 of 20 nM, cellular activity of 90 nM, and &gt;100-fold selectivity over related aspartyl proteases. Acute oral administration of (R)-37 at 30 mg/kg resulted in a significant 71% reduction of plasma Abeta40 measured at the 6 h time point in a Tg2576 mouse model (p &lt; 0.001).
-
===Bace-1 with Compound 3===
+
Aminoimidazoles as potent and selective human beta-secretase (BACE1) inhibitors.,Malamas MS, Erdei J, Gunawan I, Barnes K, Johnson M, Hui Y, Turner J, Hu Y, Wagner E, Fan K, Olland A, Bard J, Robichaud AJ J Med Chem. 2009 Oct 22;52(20):6314-23. PMID:19757823<ref>PMID:19757823</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3igb" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_19757823}}, 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 19757823 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_19757823}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
3IGB 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=3IGB OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:19757823</ref><references group="xtra"/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Memapsin 2]]
+
[[Category: Large Structures]]
-
[[Category: Olland, A M.]]
+
[[Category: Olland AM]]
-
[[Category: Alternative splicing]]
+
-
[[Category: Amino-imidazole]]
+
-
[[Category: Aspartyl protease]]
+
-
[[Category: Bace-1]]
+
-
[[Category: Disulfide bond]]
+
-
[[Category: Glycoprotein]]
+
-
[[Category: Hydrolase]]
+
-
[[Category: Inhibitor]]
+
-
[[Category: Membrane]]
+
-
[[Category: Polymorphism]]
+
-
[[Category: Protease]]
+
-
[[Category: Structure]]
+
-
[[Category: Transmembrane]]
+
-
[[Category: Zymogen]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 28 15:14:04 2010''
+

Current revision

Bace-1 with Compound 3

PDB ID 3igb

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/3igb"
Personal tools