1gsf
From Proteopedia
(New page: 200px<br /> <applet load="1gsf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gsf, resolution 2.7Å" /> '''GLUTATHIONE TRANSFER...) |
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| - | [[Image:1gsf.gif|left|200px]]<br /> | + | [[Image:1gsf.gif|left|200px]]<br /><applet load="1gsf" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gsf" size=" | + | |
caption="1gsf, resolution 2.7Å" /> | caption="1gsf, resolution 2.7Å" /> | ||
'''GLUTATHIONE TRANSFERASE A1-1 COMPLEXED WITH ETHACRYNIC ACID'''<br /> | '''GLUTATHIONE TRANSFERASE A1-1 COMPLEXED WITH ETHACRYNIC ACID'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Glutathione transferases (GSTs) constitute a family of | + | BACKGROUND: Glutathione transferases (GSTs) constitute a family of isoenzymes that catalyze the conjugation of the tripeptide glutathione with a wide variety of hydrophobic compounds bearing an electrophilic functional group. Recently, a number of X-ray structures have been reported which have defined both the glutathione- and the substrate-binding sites in these enzymes. The structure of the glutathione-free enzyme from a mammalian source has not, however, been reported previously. RESULTS: We have solved structures of a human alpha-class GST, isoenzyme A1-1, both in the unliganded form and in complexes with the inhibitor ethacrynic acid and its glutathione conjugate. These structures have been refined to resolutions of 2.5 A, 2.7 A and 2.0 A respectively. Both forms of the inhibitor are clearly present in the associated electron density. CONCLUSIONS: The major differences among the three structures reported here involve the C-terminal alpha-helix, which is a characteristic of the alpha-class enzyme. This helix forms a lid over the active site when the hydrophobic substrate binding site (H-site) is occupied but it is otherwise disordered. Ethacrynic acid appears to bind in a non-productive mode in the absence of the coenzyme glutathione. |
==About this Structure== | ==About this Structure== | ||
| - | 1GSF 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 EAA 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:// | + | 1GSF 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=EAA:'>EAA</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=1GSF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cameron, A | + | [[Category: Cameron, A D.]] |
| - | [[Category: Hermite, G | + | [[Category: Hermite, G L.]] |
| - | [[Category: Jones, T | + | [[Category: Jones, T A.]] |
[[Category: Sinning, I.]] | [[Category: Sinning, I.]] | ||
[[Category: EAA]] | [[Category: EAA]] | ||
[[Category: a1-1]] | [[Category: a1-1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:53:25 2008'' |
Revision as of 10:53, 21 February 2008
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GLUTATHIONE TRANSFERASE A1-1 COMPLEXED WITH ETHACRYNIC ACID
Overview
BACKGROUND: Glutathione transferases (GSTs) constitute a family of isoenzymes that catalyze the conjugation of the tripeptide glutathione with a wide variety of hydrophobic compounds bearing an electrophilic functional group. Recently, a number of X-ray structures have been reported which have defined both the glutathione- and the substrate-binding sites in these enzymes. The structure of the glutathione-free enzyme from a mammalian source has not, however, been reported previously. RESULTS: We have solved structures of a human alpha-class GST, isoenzyme A1-1, both in the unliganded form and in complexes with the inhibitor ethacrynic acid and its glutathione conjugate. These structures have been refined to resolutions of 2.5 A, 2.7 A and 2.0 A respectively. Both forms of the inhibitor are clearly present in the associated electron density. CONCLUSIONS: The major differences among the three structures reported here involve the C-terminal alpha-helix, which is a characteristic of the alpha-class enzyme. This helix forms a lid over the active site when the hydrophobic substrate binding site (H-site) is occupied but it is otherwise disordered. Ethacrynic acid appears to bind in a non-productive mode in the absence of the coenzyme glutathione.
About this Structure
1GSF 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
Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate., Cameron AD, Sinning I, L'Hermite G, Olin B, Board PG, Mannervik B, Jones TA, Structure. 1995 Jul 15;3(7):717-27. PMID:8591048
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