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.


1aqw

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:32, 7 February 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1aqw.gif|left|200px]]<br /><applet load="1aqw" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1aqw, resolution 1.8&Aring;" />
 
-
'''GLUTATHIONE S-TRANSFERASE IN COMPLEX WITH GLUTATHIONE'''<br />
 
-
==Overview==
+
==GLUTATHIONE S-TRANSFERASE IN COMPLEX WITH GLUTATHIONE==
-
BACKGROUND: Glutathione S-transferases (GSTs) are detoxification enzymes, found in all aerobic organisms, which catalyse the conjugation of glutathione with a wide range of hydrophobic electrophilic substrates, thereby protecting the cell from serious damage caused by electrophilic compounds. GSTs are classified into five distinct classes (alpha, mu, pi, sigma and theta) by their substrate specificity and primary structure. Human GSTs are of interest because tumour cells show increased levels of expression of single classes of GSTs, which leads to drug resistance. Structural differences between classes of GST can therefore be utilised to develop new anti-cancer drugs. Many mutational and structural studies have been carried out on the mu and alpha classes of GST to elucidate the reaction mechanism, whereas knowledge about the pi class is still limited. RESULTS: We have solved the structures of the pi class GST hP1-1 in complex with its substrate, glutathione, a transition-state complex, the Meisenheimer complex, and an inhibitor, S-(rho-bromobenzyl)-glutathione, and refined them to resolutions of 1.8 A, 2.0 A and 1.9 A, respectively. All ligand molecules are well-defined in the electron density. In all three structures, an additionally bound N-morpholino-ethansulfonic acid molecule from the buffer solution was found. CONCLUSIONS: In the structure of the GST-glutathione complex, two conserved water molecules are observed, one of which hydrogen bonds directly to the sulphur atom of glutathione and the other forms hydrogen bonds with residues around the glutathione-binding site. These water molecules are absent from the structure of the Meisenheimer complex bound to GST, implicating that deprotonation of the cysteine occurs during formation of the ternary complex which involves expulsion of the inner bound water molecule. The comparison of our structures with known mu class GST structures show differences in the location of the electrophile-binding site (H-site), explaining the different substrate specificities of the two classes. Fluorescence measurements are in agreement with the position of the N-morpholino-ethansulfonic acid, close to Trp28, identifying a possible ligandin-substrate binding site.
+
<StructureSection load='1aqw' size='340' side='right'caption='[[1aqw]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1aqw]] is a 4 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=1AQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AQW FirstGlance]. <br>
 +
</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></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=1aqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aqw OCA], [https://pdbe.org/1aqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aqw RCSB], [https://www.ebi.ac.uk/pdbsum/1aqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aqw 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/aq/1aqw_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=1aqw ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1AQW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AQW OCA].
+
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor., Prade L, Huber R, Manoharan TH, Fahl WE, Reuter W, Structure. 1997 Oct 15;5(10):1287-95. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9351803 9351803]
+
__TOC__
-
[[Category: Glutathione transferase]]
+
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Fahl, W E.]]
+
[[Category: Fahl WE]]
-
[[Category: Huber, R.]]
+
[[Category: Huber R]]
-
[[Category: Manoharan, T H.]]
+
[[Category: Manoharan TH]]
-
[[Category: Prade, L.]]
+
[[Category: Prade L]]
-
[[Category: Reuter, W.]]
+
[[Category: Reuter W]]
-
[[Category: MES]]
+
-
[[Category: class pi]]
+
-
[[Category: glutathione s-transferase]]
+
-
[[Category: transferase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:47:21 2008''
+

Current revision

GLUTATHIONE S-TRANSFERASE IN COMPLEX WITH GLUTATHIONE

PDB ID 1aqw

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/1aqw"
Personal tools