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.


1tdi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:28, 23 August 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1tdi.gif|left|200px]]
 
-
<!--
+
==Crystal Structure of hGSTA3-3 in Complex with Glutathione==
-
The line below this paragraph, containing "STRUCTURE_1tdi", creates the "Structure Box" on the page.
+
<StructureSection load='1tdi' size='340' side='right'caption='[[1tdi]], [[Resolution|resolution]] 2.40&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'>[[1tdi]] 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=1TDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TDI 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]] 2.4&#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></td></tr>
-
{{STRUCTURE_1tdi| PDB=1tdi | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdi OCA], [https://pdbe.org/1tdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tdi RCSB], [https://www.ebi.ac.uk/pdbsum/1tdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tdi ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/GSTA3_HUMAN GSTA3_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.<ref>PMID:15595823</ref> <ref>PMID:20083122</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/td/1tdi_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=1tdi ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The crystal structure of human class alpha glutathione (GSH) S-transferase A3-3 (hGSTA3-3) in complex with GSH was determined at 2.4 A. Despite considerable amino acid sequence identity with other human class alpha GSTs (e.g., hGSTA1-1), hGSTA3-3 is unique due to its exceptionally high steroid double bond isomerase activity for the transformation of Delta(5)-androstene-3,17-dione (Delta(5)-AD) to Delta(4)-androstene-3,17-dione. A comparative analysis of the active centers of hGSTA1-1 and hGSTA3-3 reveals that residues in positions 12 and 208 may contribute to their disparate isomerase activity toward Delta(5)-AD. Substitution of these two residues of hGSTA3-3 with the corresponding residues in hGSTA1-1 followed by kinetic characterization of the wild-type and the mutant enzymes supported this prediction. On the basis of our model of the hGSTA3-3.GSH.Delta(5)-AD ternary complex and available biochemical data, we propose that the thiolate group of deprotonated GSH (GS(-)) serves as a base to initiate the reaction by accepting a proton from the steroid and the nonionized hydroxyl group of catalytic residue Y9 (HO-Y9) functions as part of a proton-conducting wire to transfer a proton back to the steroid. Residue R15 may function to stabilize the deprotonated thiolate group of GSH (GS(-)), and a GSH-bound water molecule may donate a hydrogen bond to the 3-keto group of Delta(5)-AD and thus help the thiolate of GS(-) to initiate the proton transfer and the subsequent stabilization of the reaction intermediate.
-
'''Crystal Structure of hGSTA3-3 in Complex with Glutathione'''
+
Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity.,Gu Y, Guo J, Pal A, Pan SS, Zimniak P, Singh SV, Ji X Biochemistry. 2004 Dec 21;43(50):15673-9. PMID:15595823<ref>PMID:15595823</ref>
-
 
+
-
 
+
-
==Overview==
+
-
The crystal structure of human class alpha glutathione (GSH) S-transferase A3-3 (hGSTA3-3) in complex with GSH was determined at 2.4 A. Despite considerable amino acid sequence identity with other human class alpha GSTs (e.g., hGSTA1-1), hGSTA3-3 is unique due to its exceptionally high steroid double bond isomerase activity for the transformation of Delta(5)-androstene-3,17-dione (Delta(5)-AD) to Delta(4)-androstene-3,17-dione. A comparative analysis of the active centers of hGSTA1-1 and hGSTA3-3 reveals that residues in positions 12 and 208 may contribute to their disparate isomerase activity toward Delta(5)-AD. Substitution of these two residues of hGSTA3-3 with the corresponding residues in hGSTA1-1 followed by kinetic characterization of the wild-type and the mutant enzymes supported this prediction. On the basis of our model of the hGSTA3-3.GSH.Delta(5)-AD ternary complex and available biochemical data, we propose that the thiolate group of deprotonated GSH (GS(-)) serves as a base to initiate the reaction by accepting a proton from the steroid and the nonionized hydroxyl group of catalytic residue Y9 (HO-Y9) functions as part of a proton-conducting wire to transfer a proton back to the steroid. Residue R15 may function to stabilize the deprotonated thiolate group of GSH (GS(-)), and a GSH-bound water molecule may donate a hydrogen bond to the 3-keto group of Delta(5)-AD and thus help the thiolate of GS(-) to initiate the proton transfer and the subsequent stabilization of the reaction intermediate.
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
1TDI 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=1TDI OCA].
+
</div>
 +
<div class="pdbe-citations 1tdi" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity., Gu Y, Guo J, Pal A, Pan SS, Zimniak P, Singh SV, Ji X, Biochemistry. 2004 Dec 21;43(50):15673-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15595823 15595823]
+
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
-
[[Category: Glutathione transferase]]
+
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Gu, Y.]]
+
[[Category: Gu Y]]
-
[[Category: Guo, J.]]
+
[[Category: Guo J]]
-
[[Category: Ji, X.]]
+
[[Category: Ji X]]
-
[[Category: Pal, A.]]
+
[[Category: Pal A]]
-
[[Category: Pan, S S.]]
+
[[Category: Pan SS]]
-
[[Category: Singh, S V.]]
+
[[Category: Singh SV]]
-
[[Category: Zimniak, P.]]
+
[[Category: Zimniak P]]
-
[[Category: Gst]]
+
-
[[Category: Hgsta3-3]]
+
-
[[Category: Steroid isomerase]]
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:49:23 2008''
+

Current revision

Crystal Structure of hGSTA3-3 in Complex with Glutathione

PDB ID 1tdi

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/1tdi"
Personal tools