1m99
From Proteopedia
(New page: 200px<br /> <applet load="1m99" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m99, resolution 2.30Å" /> '''Crystal structure o...) |
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caption="1m99, resolution 2.30Å" /> | caption="1m99, resolution 2.30Å" /> | ||
'''Crystal structure of the 26 kDa glutathione S-transferase from Schistosoma japonicum complexed with glutathione sulfonic acid'''<br /> | '''Crystal structure of the 26 kDa glutathione S-transferase from Schistosoma japonicum complexed with glutathione sulfonic acid'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 26-kDa glutathione S-transferase from Schistosoma japonicum (Sj26GST), a helminth worm that causes schistosomiasis, catalyzes the conjugation of | + | The 26-kDa glutathione S-transferase from Schistosoma japonicum (Sj26GST), a helminth worm that causes schistosomiasis, catalyzes the conjugation of glutathione with toxic secondary products of membrane lipid peroxidation. Crystal structures of Sj26GST in complex with glutathione sulfonate (Sj26GSTSLF), S-hexyl glutathione (Sj26GSTHEX), and S-2-iodobenzyl glutathione (Sj26GSTIBZ) allow characterization of the electrophile binding site (H site) of Sj26GST. The S-hexyl and S-2-iodobenzyl moieties of these product analogs bind in a pocket defined by side-chains from the beta1-alpha1 loop (Tyr7, Trp8, Ile10, Gly12, Leu13), helix alpha4 (Arg103, Tyr104, Ser107, Tyr111), and the C-terminal coil (Gln204, Gly205, Trp206, Gln207). Changes in the Ser107 and Gln204 dihedral angles make the H site more hydrophobic in the Sj26GSTHEX complex relative to the ligand-free structure. These structures, together with docking studies, indicate a possible binding mode of Sj26GST to its physiologic substrates 4-hydroxynon-2-enal (4HNE), trans-non-2-enal (NE), and ethacrynic acid (EA). In this binding mode, hydrogen bonds of Tyr111 and Gln207 to the carbonyl oxygen atoms of 4HNE, NE, and EA could orient the substrates and enhance their electrophilicity to promote conjugation with glutathione. |
==About this Structure== | ==About this Structure== | ||
| - | 1M99 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum] with GTS 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:// | + | 1M99 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum] with <scene name='pdbligand=GTS:'>GTS</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=1M99 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Schistosoma japonicum]] | [[Category: Schistosoma japonicum]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bruns, C | + | [[Category: Bruns, C M.]] |
| - | [[Category: Cardoso, R | + | [[Category: Cardoso, R M.F.]] |
| - | [[Category: Daniels, D | + | [[Category: Daniels, D S.]] |
| - | [[Category: Tainer, J | + | [[Category: Tainer, J A.]] |
[[Category: GTS]] | [[Category: GTS]] | ||
[[Category: antigen]] | [[Category: antigen]] | ||
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[[Category: multigene family]] | [[Category: multigene family]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:52:51 2008'' |
Revision as of 11:52, 21 February 2008
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Crystal structure of the 26 kDa glutathione S-transferase from Schistosoma japonicum complexed with glutathione sulfonic acid
Overview
The 26-kDa glutathione S-transferase from Schistosoma japonicum (Sj26GST), a helminth worm that causes schistosomiasis, catalyzes the conjugation of glutathione with toxic secondary products of membrane lipid peroxidation. Crystal structures of Sj26GST in complex with glutathione sulfonate (Sj26GSTSLF), S-hexyl glutathione (Sj26GSTHEX), and S-2-iodobenzyl glutathione (Sj26GSTIBZ) allow characterization of the electrophile binding site (H site) of Sj26GST. The S-hexyl and S-2-iodobenzyl moieties of these product analogs bind in a pocket defined by side-chains from the beta1-alpha1 loop (Tyr7, Trp8, Ile10, Gly12, Leu13), helix alpha4 (Arg103, Tyr104, Ser107, Tyr111), and the C-terminal coil (Gln204, Gly205, Trp206, Gln207). Changes in the Ser107 and Gln204 dihedral angles make the H site more hydrophobic in the Sj26GSTHEX complex relative to the ligand-free structure. These structures, together with docking studies, indicate a possible binding mode of Sj26GST to its physiologic substrates 4-hydroxynon-2-enal (4HNE), trans-non-2-enal (NE), and ethacrynic acid (EA). In this binding mode, hydrogen bonds of Tyr111 and Gln207 to the carbonyl oxygen atoms of 4HNE, NE, and EA could orient the substrates and enhance their electrophilicity to promote conjugation with glutathione.
About this Structure
1M99 is a Single protein structure of sequence from Schistosoma japonicum with as ligand. Active as Glutathione transferase, with EC number 2.5.1.18 Full crystallographic information is available from OCA.
Reference
Characterization of the electrophile binding site and substrate binding mode of the 26-kDa glutathione S-transferase from Schistosoma japonicum., Cardoso RM, Daniels DS, Bruns CM, Tainer JA, Proteins. 2003 Apr 1;51(1):137-46. PMID:12596270
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