2hnl
From Proteopedia
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[[Image:2hnl.jpg|left|200px]] | [[Image:2hnl.jpg|left|200px]] | ||
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| - | | | + | {{STRUCTURE_2hnl| PDB=2hnl | SCENE= }} |
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'''Structure of the prostaglandin D synthase from the parasitic nematode Onchocerca volvulus''' | '''Structure of the prostaglandin D synthase from the parasitic nematode Onchocerca volvulus''' | ||
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| + | ==Overview== | ||
| + | Onchocerciasis or river blindness, caused by the filarial worm Onchocerca volvulus, is the world's second leading infectious cause of blindness. In order to chronically infect the host, O. volvulus has evolved molecular strategies that influence and direct immune responses away from the modes most damaging to it. The O. volvulus GST1 (OvGST1) is a unique glutathione S-transferase (GST) in that it is a glycoprotein and possesses a signal peptide that is cleaved off in the process of maturation. The mature protein starts with a 25-amino-acid extension not present in other GSTs. In all life stages of the filarial worm, it is located directly at the parasite-host interface. Here, the OvGST1 functions as a highly specific glutathione-dependent prostaglandin D synthase (PGDS). The enzyme therefore has the potential to participate in the modulation of immune responses by contributing to the production of parasite-derived prostanoids and restraining the host's effector responses, making it a tempting target for chemotherapy and vaccine development. Here, we report the crystal structure of the OvGST1 bound to its cofactor glutathione at 2.0 A resolution. The structure reveals an overall structural homology to the haematopoietic PGDS from vertebrates but, surprisingly, also a large conformational change in the prostaglandin binding pocket. The observed differences reveal a different vicinity of the prostaglandin H(2) binding pocket that demands another prostaglandin H(2) binding mode to that proposed for the vertebrate PGDS. Finally, a putative substrate binding mode for prostaglandin H(2) is postulated based on the observed structural insights. | ||
==About this Structure== | ==About this Structure== | ||
2HNL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Onchocerca_volvulus Onchocerca volvulus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HNL OCA]. | 2HNL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Onchocerca_volvulus Onchocerca volvulus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HNL OCA]. | ||
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| + | ==Reference== | ||
| + | Structure of the extracellular glutathione S-transferase OvGST1 from the human pathogenic parasite Onchocerca volvulus., Perbandt M, Hoppner J, Burmeister C, Luersen K, Betzel C, Liebau E, J Mol Biol. 2008 Mar 21;377(2):501-11. Epub 2008 Jan 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18258257 18258257] | ||
[[Category: Glutathione transferase]] | [[Category: Glutathione transferase]] | ||
[[Category: Onchocerca volvulus]] | [[Category: Onchocerca volvulus]] | ||
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[[Category: Liebau, E.]] | [[Category: Liebau, E.]] | ||
[[Category: Perbandt, M.]] | [[Category: Perbandt, M.]] | ||
| - | [[Category: | + | [[Category: Glutathione s-transferase]] |
| - | [[Category: | + | [[Category: Immune modulation]] |
| - | [[Category: | + | [[Category: Onchocerca volvulus]] |
| - | [[Category: | + | [[Category: Prostaglandin synthase]] |
| - | [[Category: | + | [[Category: River blindness]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 16 23:06:33 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 20:06, 16 April 2008
Structure of the prostaglandin D synthase from the parasitic nematode Onchocerca volvulus
Overview
Onchocerciasis or river blindness, caused by the filarial worm Onchocerca volvulus, is the world's second leading infectious cause of blindness. In order to chronically infect the host, O. volvulus has evolved molecular strategies that influence and direct immune responses away from the modes most damaging to it. The O. volvulus GST1 (OvGST1) is a unique glutathione S-transferase (GST) in that it is a glycoprotein and possesses a signal peptide that is cleaved off in the process of maturation. The mature protein starts with a 25-amino-acid extension not present in other GSTs. In all life stages of the filarial worm, it is located directly at the parasite-host interface. Here, the OvGST1 functions as a highly specific glutathione-dependent prostaglandin D synthase (PGDS). The enzyme therefore has the potential to participate in the modulation of immune responses by contributing to the production of parasite-derived prostanoids and restraining the host's effector responses, making it a tempting target for chemotherapy and vaccine development. Here, we report the crystal structure of the OvGST1 bound to its cofactor glutathione at 2.0 A resolution. The structure reveals an overall structural homology to the haematopoietic PGDS from vertebrates but, surprisingly, also a large conformational change in the prostaglandin binding pocket. The observed differences reveal a different vicinity of the prostaglandin H(2) binding pocket that demands another prostaglandin H(2) binding mode to that proposed for the vertebrate PGDS. Finally, a putative substrate binding mode for prostaglandin H(2) is postulated based on the observed structural insights.
About this Structure
2HNL is a Single protein structure of sequence from Onchocerca volvulus. Full crystallographic information is available from OCA.
Reference
Structure of the extracellular glutathione S-transferase OvGST1 from the human pathogenic parasite Onchocerca volvulus., Perbandt M, Hoppner J, Burmeister C, Luersen K, Betzel C, Liebau E, J Mol Biol. 2008 Mar 21;377(2):501-11. Epub 2008 Jan 16. PMID:18258257 Page seeded by OCA on Wed Apr 16 23:06:33 2008
