2wf4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:54, 7 July 2021) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2wf4.png|left|200px]]
 
-
{{STRUCTURE_2wf4| PDB=2wf4 | SCENE= }}
+
==Human BACE-1 in complex with 6-ethyl-1-methyl-N-((1S)-2-oxo-1-(phenylmethyl)-3-(tetrahydro-2H-pyran-4-ylamino)propyl)-1,3,4,6- tetrahydro(1,2)thiazepino(5,4,3-cd)indole-8-carboxamide 2,2-dioxide==
 +
<StructureSection load='2wf4' size='340' side='right'caption='[[2wf4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2wf4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WF4 FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZY4:N-[(1S)-1-BENZYL-2,2-DIHYDROXY-3-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PROPYL]-6-ETHYL-1-METHYL-1,3,4,6-TETRAHYDRO[1,2]THIAZEPINO[5,4,3-CD]INDOLE-8-CARBOXAMIDE+2,2-DIOXIDE'>ZY4</scene></td></tr>
 +
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1tqf|1tqf]], [[1xn3|1xn3]], [[1m4h|1m4h]], [[2vnm|2vnm]], [[2fdp|2fdp]], [[1xn2|1xn2]], [[2viy|2viy]], [[2va6|2va6]], [[2vie|2vie]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vkm|2vkm]], [[2vj9|2vj9]], [[2vnn|2vnn]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[2vj7|2vj7]], [[1w51|1w51]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2wf0|2wf0]], [[2wez|2wez]], [[2wf2|2wf2]]</div></td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></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=2wf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wf4 OCA], [https://pdbe.org/2wf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wf4 RCSB], [https://www.ebi.ac.uk/pdbsum/2wf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wf4 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/wf/2wf4_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2wf4 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration.
-
===HUMAN BACE-1 IN COMPLEX WITH 6-ETHYL-1-METHYL-N-((1S)-2-OXO-1-(PHENYLMETHYL)-3-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PROPYL)-1,3,4,6-TETRAHYDRO(1,2)THIAZEPINO(5,4,3-CD)INDOLE-8-CARBOXAMIDE 2,2-DIOXIDE===
+
Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G Bioorg Med Chem Lett. 2009 Jul 1;19(13):3674-8. Epub 2009 Apr 5. PMID:19406640<ref>PMID:19406640</ref>
-
{{ABSTRACT_PUBMED_19406640}}
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
==About this Structure==
+
<div class="pdbe-citations 2wf4" style="background-color:#fffaf0;"></div>
-
[[2wf4]] 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=2WF4 OCA].
+
==See Also==
==See Also==
-
*[[Beta secretase|Beta secretase]]
+
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:019406640</ref><references group="xtra"/>
+
__TOC__
-
[[Category: Homo sapiens]]
+
</StructureSection>
 +
[[Category: Human]]
 +
[[Category: Large Structures]]
[[Category: Memapsin 2]]
[[Category: Memapsin 2]]
-
[[Category: Brien, A O.]]
+
[[Category: Brien, A O]]
-
[[Category: Charrier, N.]]
+
[[Category: Charrier, N]]
-
[[Category: Clarke, B.]]
+
[[Category: Clarke, B]]
-
[[Category: Cutler, L.]]
+
[[Category: Cutler, L]]
-
[[Category: Demont, E.]]
+
[[Category: Demont, E]]
-
[[Category: Dingwall, C.]]
+
[[Category: Dingwall, C]]
-
[[Category: Dunsdon, R.]]
+
[[Category: Dunsdon, R]]
-
[[Category: Hawkins, J.]]
+
[[Category: Hawkins, J]]
-
[[Category: Howes, C.]]
+
[[Category: Howes, C]]
-
[[Category: Hubbard, J.]]
+
[[Category: Hubbard, J]]
-
[[Category: Hussain, I.]]
+
[[Category: Hussain, I]]
-
[[Category: Maile, G.]]
+
[[Category: Maile, G]]
-
[[Category: Matico, R.]]
+
[[Category: Matico, R]]
-
[[Category: Mosley, J.]]
+
[[Category: Mosley, J]]
-
[[Category: Naylor, A.]]
+
[[Category: Naylor, A]]
-
[[Category: Redshaw, S.]]
+
[[Category: Redshaw, S]]
-
[[Category: Rowland, P.]]
+
[[Category: Rowland, P]]
-
[[Category: Smith, K J.]]
+
[[Category: Smith, K J]]
-
[[Category: Soleil, V.]]
+
[[Category: Soleil, V]]
-
[[Category: Sweitzer, S.]]
+
[[Category: Sweitzer, S]]
-
[[Category: Theobald, P.]]
+
[[Category: Theobald, P]]
-
[[Category: Vesey, D.]]
+
[[Category: Vesey, D]]
-
[[Category: Walter, D S.]]
+
[[Category: Walter, D S]]
-
[[Category: Wayne, G.]]
+
[[Category: Wayne, G]]
 +
[[Category: Alternative splicing]]
[[Category: Asp-2]]
[[Category: Asp-2]]
[[Category: Aspartyl protease]]
[[Category: Aspartyl protease]]
Line 51: Line 75:
[[Category: Memapsin-2]]
[[Category: Memapsin-2]]
[[Category: Membrane]]
[[Category: Membrane]]
 +
[[Category: Polymorphism]]
[[Category: Protease]]
[[Category: Protease]]
[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Zymogen]]
[[Category: Zymogen]]

Current revision

Human BACE-1 in complex with 6-ethyl-1-methyl-N-((1S)-2-oxo-1-(phenylmethyl)-3-(tetrahydro-2H-pyran-4-ylamino)propyl)-1,3,4,6- tetrahydro(1,2)thiazepino(5,4,3-cd)indole-8-carboxamide 2,2-dioxide

PDB ID 2wf4

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/2wf4"
Personal tools