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1tdi

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Revision as of 13:12, 21 February 2008

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Crystal Structure of hGSTA3-3 in Complex with Glutathione

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

1TDI is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Glutathione transferase, with EC number 2.5.1.18 Full crystallographic information is available from OCA.

Reference

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

Page seeded by OCA on Thu Feb 21 15:12:24 2008

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Retrieved from "http://52.214.119.220/wiki/index.php/1tdi"

@@ Line 1: / Line 1: @@
-[[Image:1tdi.gif|left|200px]]<br />
+[[Image:1tdi.gif|left|200px]]<br /><applet load="1tdi" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1tdi" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1tdi, resolution 2.40&Aring;" />
 '''Crystal Structure of hGSTA3-3 in Complex with Glutathione'''<br />
 ==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.
+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==
-TDI 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 GSH 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TDI OCA].
+TDI 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=GSH:'>GSH</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=1TDI OCA].
 ==Reference==
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 [[Category: Ji, X.]]
 [[Category: Pal, A.]]
-[[Category: Pan, S.S.]]
+[[Category: Pan, S S.]]
-[[Category: Singh, S.V.]]
+[[Category: Singh, S V.]]
 [[Category: Zimniak, P.]]
 [[Category: GSH]]
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 [[Category: steroid isomerase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:23:32 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:12:24 2008''

1tdi

From Proteopedia

Revision as of 13:12, 21 February 2008

Overview

About this Structure

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