1gsd
From Proteopedia
(New page: 200px<br /> <applet load="1gsd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gsd, resolution 2.5Å" /> '''GLUTATHIONE TRANSFER...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1gsd.gif|left|200px]]<br /> | + | [[Image:1gsd.gif|left|200px]]<br /><applet load="1gsd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gsd" size=" | + | |
caption="1gsd, resolution 2.5Å" /> | caption="1gsd, resolution 2.5Å" /> | ||
'''GLUTATHIONE TRANSFERASE A1-1 IN UNLIGANDED FORM'''<br /> | '''GLUTATHIONE TRANSFERASE A1-1 IN UNLIGANDED FORM'''<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== | ||
| - | 1GSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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:// | + | 1GSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=1GSD OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 14: | ||
[[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: transferase (glutathione)]] | [[Category: transferase (glutathione)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:53:24 2008'' |
Revision as of 10:53, 21 February 2008
|
GLUTATHIONE TRANSFERASE A1-1 IN UNLIGANDED FORM
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
1GSD is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Thu Feb 21 12:53:24 2008
