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1tdi

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{{STRUCTURE_1tdi| PDB=1tdi | SCENE= }}
{{STRUCTURE_1tdi| PDB=1tdi | SCENE= }}
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'''Crystal Structure of hGSTA3-3 in Complex with Glutathione'''
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===Crystal Structure of hGSTA3-3 in Complex with Glutathione===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15595823 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15595823}}
==About this Structure==
==About this Structure==
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[[Category: Hgsta3-3]]
[[Category: Hgsta3-3]]
[[Category: Steroid isomerase]]
[[Category: Steroid isomerase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:56:39 2008''

Revision as of 21:56, 27 July 2008

Template:STRUCTURE 1tdi

Crystal Structure of hGSTA3-3 in Complex with Glutathione

Template:ABSTRACT PUBMED 15595823

About this Structure

1TDI is a Single protein structure of sequence from Homo sapiens. 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

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