1u87
From Proteopedia
(New page: 200px<br /><applet load="1u87" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u87, resolution 3.50Å" /> '''Crystal Structure Of...) |
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| - | [[Image:1u87.gif|left|200px]]<br /><applet load="1u87" size=" | + | [[Image:1u87.gif|left|200px]]<br /><applet load="1u87" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1u87, resolution 3.50Å" /> | caption="1u87, resolution 3.50Å" /> | ||
'''Crystal Structure Of The 26 Kda Glutathione S-Transferase Y7F mutant From Schistosoma Japonicum Complexed With Glutathione'''<br /> | '''Crystal Structure Of The 26 Kda Glutathione S-Transferase Y7F mutant From Schistosoma Japonicum Complexed With Glutathione'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Glutathione S-transferases are a family of multifunctional enzymes | + | Glutathione S-transferases are a family of multifunctional enzymes involved in the metabolism of drugs and xenobiotics. Two tyrosine residues, Tyr 7 and Tyr 111, in the active site of the enzyme play an important role in the binding and catalysis of substrate ligands. The crystal structures of Schistosoma japonicum glutathione S-transferase tyrosine 7 to phenylalanine mutant [SjGST(Y7F)] in complex with the substrate glutathione (GSH) and the competitive inhibitor S-octylglutathione (S-octyl-GSH) have been obtained. These new structural data combined with fluorescence spectroscopy and thermodynamic data, obtained by means of isothermal titration calorimetry, allow for detailed characterization of the ligand-binding process. The binding of S-octyl-GSH to SjGST(Y7F) is enthalpically and entropically driven at temperatures below 30 degrees C. The stoichiometry of the binding is one molecule of S-octyl-GSH per mutant dimer, whereas shorter alkyl derivatives bind with a stoichiometry of two molecules per mutant dimer. The SjGST(Y7F).GSH structure showed no major structural differences compared to the wild-type enzyme. In contrast, the structure of SjGST(Y7F).S-octyl-GSH showed asymmetric binding of S-octyl-GSH. This lack of symmetry is reflected in the lower symmetry space group of the SjGST(Y7F).S-octyl-GSH crystals (P6(3)) compared to that of the SjGST(Y7F).GSH crystals (P6(3)22). Moreover, the binding of S-octyl-GSH to the A subunit is accompanied by conformational changes that may be responsible for the lack of binding to the B subunit. |
==About this Structure== | ==About this Structure== | ||
| - | 1U87 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 GSW 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:// | + | 1U87 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=GSW:'>GSW</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=1U87 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Camara-Artigas, A.]] | [[Category: Camara-Artigas, A.]] | ||
| - | [[Category: Smith, A | + | [[Category: Smith, A W.]] |
[[Category: GSW]] | [[Category: GSW]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:21:34 2008'' |
Revision as of 13:21, 21 February 2008
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Crystal Structure Of The 26 Kda Glutathione S-Transferase Y7F mutant From Schistosoma Japonicum Complexed With Glutathione
Overview
Glutathione S-transferases are a family of multifunctional enzymes involved in the metabolism of drugs and xenobiotics. Two tyrosine residues, Tyr 7 and Tyr 111, in the active site of the enzyme play an important role in the binding and catalysis of substrate ligands. The crystal structures of Schistosoma japonicum glutathione S-transferase tyrosine 7 to phenylalanine mutant [SjGST(Y7F)] in complex with the substrate glutathione (GSH) and the competitive inhibitor S-octylglutathione (S-octyl-GSH) have been obtained. These new structural data combined with fluorescence spectroscopy and thermodynamic data, obtained by means of isothermal titration calorimetry, allow for detailed characterization of the ligand-binding process. The binding of S-octyl-GSH to SjGST(Y7F) is enthalpically and entropically driven at temperatures below 30 degrees C. The stoichiometry of the binding is one molecule of S-octyl-GSH per mutant dimer, whereas shorter alkyl derivatives bind with a stoichiometry of two molecules per mutant dimer. The SjGST(Y7F).GSH structure showed no major structural differences compared to the wild-type enzyme. In contrast, the structure of SjGST(Y7F).S-octyl-GSH showed asymmetric binding of S-octyl-GSH. This lack of symmetry is reflected in the lower symmetry space group of the SjGST(Y7F).S-octyl-GSH crystals (P6(3)) compared to that of the SjGST(Y7F).GSH crystals (P6(3)22). Moreover, the binding of S-octyl-GSH to the A subunit is accompanied by conformational changes that may be responsible for the lack of binding to the B subunit.
About this Structure
1U87 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
Crystallographic and thermodynamic analysis of the binding of S-octylglutathione to the Tyr 7 to Phe mutant of glutathione S-transferase from Schistosoma japonicum., Andujar-Sanchez M, Smith AW, Clemente-Jimenez JM, Rodriguez-Vico F, Las Heras-Vazquez FJ, Jara-Perez V, Camara-Artigas A, Biochemistry. 2005 Feb 1;44(4):1174-83. PMID:15667211
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