1tu8: Difference between revisions

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[[Image:1tu8.gif|left|200px]]<br /><applet load="1tu8" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1tu8.gif|left|200px]]<br /><applet load="1tu8" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1tu8, resolution 1.80Å" />

'''STructure of Onchoverca volvulus Pi-class Glutathione S-transferase with its kompetitive inhibitor s-hexyl-GSH'''<br />

==Overview==

Onchocerciasis is a debilitating parasitic disease caused by the filarial, worm Onchocerca volvulus. Similar to other helminth parasites, O. volvulus, is capable of evading the host's immune responses by a variety of defense, mechanisms, including the detoxification activities of the glutathione, S-transferases (GSTs). Additionally, in response to drug treatment, helminth GSTs are highly up-regulated, making them tempting targets both, for chemotherapy and for vaccine development. We analyzed the, three-dimensional x-ray structure of the major cytosolic GST from O., volvulus (Ov-GST2) in complex with its natural substrate glutathione and, its competitive inhibitor S-hexylglutathione at 1.5 and 1.8 angstrom, resolution, respectively. From the perspective of the biochemical, classification, the Ov-GST2 seems to be related to pi-class GSTs. However, in comparison to other pi-class GSTs, in particular to the host's, counterpart, the Ov-GST2 reveals significant and unusual differences in, the sequence and overall structure. Major differences can be found in, helix alpha-2, an important region for substrate recognition. Moreover, the binding site for the electrophilic co-substrate is spatially increased, and more solvent-accessible. These structural alterations are responsible, for different substrate specificities and will form the basis of, parasite-specific structure-based drug design investigations.

Onchocerciasis is a debilitating parasitic disease caused by the filarial worm Onchocerca volvulus. Similar to other helminth parasites, O. volvulus is capable of evading the host's immune responses by a variety of defense mechanisms, including the detoxification activities of the glutathione S-transferases (GSTs). Additionally, in response to drug treatment, helminth GSTs are highly up-regulated, making them tempting targets both for chemotherapy and for vaccine development. We analyzed the three-dimensional x-ray structure of the major cytosolic GST from O. volvulus (Ov-GST2) in complex with its natural substrate glutathione and its competitive inhibitor S-hexylglutathione at 1.5 and 1.8 angstrom resolution, respectively. From the perspective of the biochemical classification, the Ov-GST2 seems to be related to pi-class GSTs. However, in comparison to other pi-class GSTs, in particular to the host's counterpart, the Ov-GST2 reveals significant and unusual differences in the sequence and overall structure. Major differences can be found in helix alpha-2, an important region for substrate recognition. Moreover, the binding site for the electrophilic co-substrate is spatially increased and more solvent-accessible. These structural alterations are responsible for different substrate specificities and will form the basis of parasite-specific structure-based drug design investigations.

==About this Structure==

1TU8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Onchocerca_volvulus Onchocerca volvulus] with GTX 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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1TU8 OCA].

1TU8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Onchocerca_volvulus Onchocerca volvulus] with <scene name='pdbligand=GTX:'>GTX</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=1TU8 OCA].

==Reference==

Line 18:

[[Category: transferase]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 03:35:~~42 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:22 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1tu8.gif|left|200px]]<br /><applet load="1tu8" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1tu8.gif|left|200px]]<br /><applet load="1tu8" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1tu8, resolution 1.80&Aring;" />
 '''STructure of Onchoverca volvulus Pi-class Glutathione S-transferase with its kompetitive inhibitor s-hexyl-GSH'''<br />
 ==Overview==
-Onchocerciasis is a debilitating parasitic disease caused by the filarial, worm Onchocerca volvulus. Similar to other helminth parasites, O. volvulus, is capable of evading the host's immune responses by a variety of defense, mechanisms, including the detoxification activities of the glutathione, S-transferases (GSTs). Additionally, in response to drug treatment, helminth GSTs are highly up-regulated, making them tempting targets both, for chemotherapy and for vaccine development. We analyzed the, three-dimensional x-ray structure of the major cytosolic GST from O., volvulus (Ov-GST2) in complex with its natural substrate glutathione and, its competitive inhibitor S-hexylglutathione at 1.5 and 1.8 angstrom, resolution, respectively. From the perspective of the biochemical, classification, the Ov-GST2 seems to be related to pi-class GSTs. However, in comparison to other pi-class GSTs, in particular to the host's, counterpart, the Ov-GST2 reveals significant and unusual differences in, the sequence and overall structure. Major differences can be found in, helix alpha-2, an important region for substrate recognition. Moreover, the binding site for the electrophilic co-substrate is spatially increased, and more solvent-accessible. These structural alterations are responsible, for different substrate specificities and will form the basis of, parasite-specific structure-based drug design investigations.
+Onchocerciasis is a debilitating parasitic disease caused by the filarial worm Onchocerca volvulus. Similar to other helminth parasites, O. volvulus is capable of evading the host's immune responses by a variety of defense mechanisms, including the detoxification activities of the glutathione S-transferases (GSTs). Additionally, in response to drug treatment, helminth GSTs are highly up-regulated, making them tempting targets both for chemotherapy and for vaccine development. We analyzed the three-dimensional x-ray structure of the major cytosolic GST from O. volvulus (Ov-GST2) in complex with its natural substrate glutathione and its competitive inhibitor S-hexylglutathione at 1.5 and 1.8 angstrom resolution, respectively. From the perspective of the biochemical classification, the Ov-GST2 seems to be related to pi-class GSTs. However, in comparison to other pi-class GSTs, in particular to the host's counterpart, the Ov-GST2 reveals significant and unusual differences in the sequence and overall structure. Major differences can be found in helix alpha-2, an important region for substrate recognition. Moreover, the binding site for the electrophilic co-substrate is spatially increased and more solvent-accessible. These structural alterations are responsible for different substrate specificities and will form the basis of parasite-specific structure-based drug design investigations.
 ==About this Structure==
-TU8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Onchocerca_volvulus Onchocerca volvulus] with GTX 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TU8 OCA].
+TU8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Onchocerca_volvulus Onchocerca volvulus] with <scene name='pdbligand=GTX:'>GTX</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=1TU8 OCA].
 ==Reference==
@@ Line 18: / Line 18: @@
 [[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:35:42 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:22 2008''