3ie3

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (15:57, 1 November 2023) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3ie3.jpg|left|200px]]
 
-
<!--
+
==Structural basis for the binding of the anti-cancer compound 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) to human glutathione S-transferases==
-
The line below this paragraph, containing "STRUCTURE_3ie3", creates the "Structure Box" on the page.
+
<StructureSection load='3ie3' size='340' side='right'caption='[[3ie3]], [[Resolution|resolution]] 1.80&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'>[[3ie3]] is a 2 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=3IE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IE3 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]] 1.8&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=N11:6-[(7-NITRO-2,1,3-BENZOXADIAZOL-4-YL)SULFANYL]HEXAN-1-OL'>N11</scene></td></tr>
-
{{STRUCTURE_3ie3| PDB=3ie3 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ie3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ie3 OCA], [https://pdbe.org/3ie3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ie3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ie3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ie3 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/GSTP1_HUMAN GSTP1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.<ref>PMID:21668448</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/ie/3ie3_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=3ie3 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Glutathione S-transferases (GST) constitute a superfamily of enzymes with diversified functions including detoxification from xenobiotics. In many human cancers, Pi class GST (GSTP1-1) is overexpressed and contributes to multidrug resistance by conjugating chemotherapeutics. In addition, GSTP1-1 displays antiapoptotic activity by interacting with c-Jun NH(2)-terminal kinase, a key regulator of apoptosis. Therefore, GSTP1-1 is considered a promising target for pharmaceutical treatment. Recently, a potent inhibitor of GSTs, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), was identified and tested on several tumor cell lines demonstrating high antiproliferative activity. To establish the structural basis of NBDHEX activity, we determined the crystal structure of NBDHEX bound to either GSTP1-1 or GSTM2-2 (mu class). NBDHEX in both cases binds to the H-site but occupies different positions. Furthermore, the compound is covalently attached to the GSH sulfur in the GSTM2-2 crystal, forming a sigma-complex, although it is bound but not conjugated in the GSTP1-1 crystal. Several differences in the H-sites of the two isozymes determine the higher affinity of NBDHEX for GSTM2-2 with respect to GSTP1-1. One such difference is the presence of Ile(104) in GSTP1-1 close to the bound NBDHEX, whereas the corresponding position is occupied by an alanine in GSTM2-2. Mutation of Ile(104) into valine is a frequent GSTP1-1 polymorphism and we show here that the Ile(104)Val and Ile(104)Ala variants display a 4-fold higher affinity for the compound. Remarkably, the GSTP1-1/Ile(104)Ala structure in complex with NBDHEX shows a considerable shift of the compound inside the H-site. These data might be useful for the development of new anticancer compounds.
-
===Structural basis for the binding of the anti-cancer compound 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) to human glutathione S-transferases===
+
Structural basis for the binding of the anticancer compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-transferases.,Federici L, Lo Sterzo C, Pezzola S, Di Matteo A, Scaloni F, Federici G, Caccuri AM Cancer Res. 2009 Oct 15;69(20):8025-34. Epub 2009 Oct 6. PMID:19808963<ref>PMID:19808963</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3ie3" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_19808963}}, adds the Publication Abstract to the page
+
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 19808963 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_19808963}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
3IE3 is a 2 chains structure of sequences 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=3IE3 OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:19808963</ref><references group="xtra"/>
+
-
[[Category: Glutathione transferase]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Caccuri, A M.]]
+
[[Category: Large Structures]]
-
[[Category: Federici, G.]]
+
[[Category: Caccuri AM]]
-
[[Category: Federici, L.]]
+
[[Category: Di Matteo A]]
-
[[Category: Matteo, A Di.]]
+
[[Category: Federici G]]
-
[[Category: Scaloni, F.]]
+
[[Category: Federici L]]
-
[[Category: Sterzo, C Lo.]]
+
[[Category: Lo Sterzo C]]
-
[[Category: Cancer treatment]]
+
[[Category: Scaloni F]]
-
[[Category: Detoxification]]
+
-
[[Category: Multidrug resistance]]
+
-
[[Category: Phosphoprotein]]
+
-
[[Category: Polymorphism]]
+
-
[[Category: Transferase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 28 13:16:09 2009''
+

Current revision

Structural basis for the binding of the anti-cancer compound 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) to human glutathione S-transferases

PDB ID 3ie3

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/3ie3"
Personal tools