2gss

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:44, 9 August 2023) (edit) (undo)
 
(12 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2gss.gif|left|200px]]
 
-
{{Structure
+
==HUMAN GLUTATHIONE S-TRANSFERASE P1-1 IN COMPLEX WITH ETHACRYNIC ACID==
-
|PDB= 2gss |SIZE=350|CAPTION= <scene name='initialview01'>2gss</scene>, resolution 1.9&Aring;
+
<StructureSection load='2gss' size='340' side='right'caption='[[2gss]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=EAA:ETHACRYNIC+ACID'>EAA</scene> and <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC ACID'>MES</scene>
+
<table><tr><td colspan='2'>[[2gss]] 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=2GSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GSS FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</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>
-
|GENE= GSTP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EAA:ETHACRYNIC+ACID'>EAA</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2gss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gss OCA], [https://pdbe.org/2gss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gss RCSB], [https://www.ebi.ac.uk/pdbsum/2gss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gss 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/gs/2gss_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=2gss ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The potent diuretic drug ethacrynic acid has been tested in clinical trials as an adjuvant in chemotherapy. Its target is the detoxifying enzyme glutathione transferase which is often found overexpressed in cancer tissues. We have solved the crystal structures of human pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate. Ethacrynic acid is found to bind in a nonproductive mode to one of the ligand binding sites of the enzyme (the H site) while the glutathione binding site (G site) is occupied by solvent molecules. There are no structural rearrangements of the G site in the absence of ligand. The structure indicates that bound glutathione is required for ethacrynic acid to dock into the H site in a productive binding mode. The binding of the ethacrynic acid-glutathione conjugate shows that the contacts of the glutathione moiety with the protein are identical to those observed in crystal structures of the enzyme with other glutathione-based substrates and inhibitors. The ethacrynic acid moiety of the conjugate binds in the H site in a fashion that has not been observed in crystal structures of other glutathione-based inhibitor complexes. The crystal structures implicate Tyr 108 as an electrophilic participant in the Michael addition of glutathione to ethacrynic acid.
-
'''HUMAN GLUTATHIONE S-TRANSFERASE P1-1 IN COMPLEX WITH ETHACRYNIC ACID'''
+
The three-dimensional structure of the human Pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate.,Oakley AJ, Rossjohn J, Lo Bello M, Caccuri AM, Federici G, Parker MW Biochemistry. 1997 Jan 21;36(3):576-85. PMID:9012673<ref>PMID:9012673</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 2gss" style="background-color:#fffaf0;"></div>
-
==Overview==
+
==See Also==
-
The potent diuretic drug ethacrynic acid has been tested in clinical trials as an adjuvant in chemotherapy. Its target is the detoxifying enzyme glutathione transferase which is often found overexpressed in cancer tissues. We have solved the crystal structures of human pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate. Ethacrynic acid is found to bind in a nonproductive mode to one of the ligand binding sites of the enzyme (the H site) while the glutathione binding site (G site) is occupied by solvent molecules. There are no structural rearrangements of the G site in the absence of ligand. The structure indicates that bound glutathione is required for ethacrynic acid to dock into the H site in a productive binding mode. The binding of the ethacrynic acid-glutathione conjugate shows that the contacts of the glutathione moiety with the protein are identical to those observed in crystal structures of the enzyme with other glutathione-based substrates and inhibitors. The ethacrynic acid moiety of the conjugate binds in the H site in a fashion that has not been observed in crystal structures of other glutathione-based inhibitor complexes. The crystal structures implicate Tyr 108 as an electrophilic participant in the Michael addition of glutathione to ethacrynic acid.
+
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
2GSS is a [[Single protein]] structure of 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=2GSS OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
The three-dimensional structure of the human Pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate., Oakley AJ, Rossjohn J, Lo Bello M, Caccuri AM, Federici G, Parker MW, Biochemistry. 1997 Jan 21;36(3):576-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9012673 9012673]
+
-
[[Category: Glutathione transferase]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Oakley, A J.]]
+
[[Category: Oakley AJ]]
-
[[Category: Parker, M W.]]
+
[[Category: Parker MW]]
-
[[Category: Rossjohn, J.]]
+
[[Category: Rossjohn J]]
-
[[Category: EAA]]
+
-
[[Category: MES]]
+
-
[[Category: SO4]]
+
-
[[Category: detoxification]]
+
-
[[Category: ethacrynic acid]]
+
-
[[Category: glutathione]]
+
-
[[Category: pi]]
+
-
[[Category: transferase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:08:38 2008''
+

Current revision

HUMAN GLUTATHIONE S-TRANSFERASE P1-1 IN COMPLEX WITH ETHACRYNIC ACID

PDB ID 2gss

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/2gss"
Personal tools