1hql
From Proteopedia
(New page: 200px<br /><applet load="1hql" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hql, resolution 2.20Å" /> '''The xenograft antige...) |
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| - | [[Image:1hql.jpg|left|200px]]<br /><applet load="1hql" size=" | + | [[Image:1hql.jpg|left|200px]]<br /><applet load="1hql" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hql, resolution 2.20Å" /> | caption="1hql, resolution 2.20Å" /> | ||
'''The xenograft antigen in complex with the B4 isolectin of Griffonia simplicifolia lectin-1'''<br /> | '''The xenograft antigen in complex with the B4 isolectin of Griffonia simplicifolia lectin-1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The shortage of organs for transplantation into human patients continues | + | The shortage of organs for transplantation into human patients continues to be a driving force behind research into the use of tissues from non-human donors, particularly pig. The primary barrier to such xenotransplantation is the reaction between natural antibodies present in humans and Old World monkeys and the Gal alpha(1-3)Gal epitope (xenograft antigen, xenoantigen) found on the cell surfaces of the donor organ. This hyperacute immune response leads ultimately to graft rejection. Because of its high specificity for the xenograft antigen, isolectin 1-B(4) from Griffonia simplicifolia (GS-1-B(4)) has been used as an immunodiagnostic reagent. Furthermore, haptens that inhibit natural antibodies also inhibit GS-1-B(4) from binding to the xenoantigen. Here we report the first x-ray crystal structure of the xenograft antigen bound to a protein (GS-1-B(4)). The three-dimensional structure was determined from orthorhombic crystals at a resolution of 2.3 A. To probe the influence of binding on ligand properties, we report also the results of molecular dynamics (MD) simulations on this complex as well as on the free ligand. The MD simulations were performed with the AMBER force-field for proteins augmented with the GLYCAM parameters for glycosides and glycoproteins. The simulations were performed for up to 10 ns in the presence of explicit solvent. Through comparison with MD simulations performed for the free ligand, it has been determined that GS-1-B(4) recognizes the lowest energy conformation of the disaccharide. In addition, the x-ray and modeling data provide clear explanations for the reported specificities of the GS-1-B(4) lectin. It is anticipated that a further understanding of the interactions involving the xenograft antigen will help in the development of therapeutic agents for application in the prevention of hyperacute xenograft rejection. |
==About this Structure== | ==About this Structure== | ||
| - | 1HQL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Griffonia_simplicifolia Griffonia simplicifolia] with MN and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1HQL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Griffonia_simplicifolia Griffonia simplicifolia] with <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HQL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Griffonia simplicifolia]] | [[Category: Griffonia simplicifolia]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Lipscomb, L | + | [[Category: Lipscomb, L A.]] |
| - | [[Category: Rose, J | + | [[Category: Rose, J P.]] |
[[Category: Tempel, W.]] | [[Category: Tempel, W.]] | ||
| - | [[Category: Woods, R | + | [[Category: Woods, R J.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: MN]] | [[Category: MN]] | ||
| Line 23: | Line 23: | ||
[[Category: xenograft antigen]] | [[Category: xenograft antigen]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:03:51 2008'' |
Revision as of 11:03, 21 February 2008
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The xenograft antigen in complex with the B4 isolectin of Griffonia simplicifolia lectin-1
Overview
The shortage of organs for transplantation into human patients continues to be a driving force behind research into the use of tissues from non-human donors, particularly pig. The primary barrier to such xenotransplantation is the reaction between natural antibodies present in humans and Old World monkeys and the Gal alpha(1-3)Gal epitope (xenograft antigen, xenoantigen) found on the cell surfaces of the donor organ. This hyperacute immune response leads ultimately to graft rejection. Because of its high specificity for the xenograft antigen, isolectin 1-B(4) from Griffonia simplicifolia (GS-1-B(4)) has been used as an immunodiagnostic reagent. Furthermore, haptens that inhibit natural antibodies also inhibit GS-1-B(4) from binding to the xenoantigen. Here we report the first x-ray crystal structure of the xenograft antigen bound to a protein (GS-1-B(4)). The three-dimensional structure was determined from orthorhombic crystals at a resolution of 2.3 A. To probe the influence of binding on ligand properties, we report also the results of molecular dynamics (MD) simulations on this complex as well as on the free ligand. The MD simulations were performed with the AMBER force-field for proteins augmented with the GLYCAM parameters for glycosides and glycoproteins. The simulations were performed for up to 10 ns in the presence of explicit solvent. Through comparison with MD simulations performed for the free ligand, it has been determined that GS-1-B(4) recognizes the lowest energy conformation of the disaccharide. In addition, the x-ray and modeling data provide clear explanations for the reported specificities of the GS-1-B(4) lectin. It is anticipated that a further understanding of the interactions involving the xenograft antigen will help in the development of therapeutic agents for application in the prevention of hyperacute xenograft rejection.
About this Structure
1HQL is a Protein complex structure of sequences from Griffonia simplicifolia with and as ligands. Full crystallographic information is available from OCA.
Reference
The xenograft antigen bound to Griffonia simplicifolia lectin 1-B(4). X-ray crystal structure of the complex and molecular dynamics characterization of the binding site., Tempel W, Tschampel S, Woods RJ, J Biol Chem. 2002 Feb 22;277(8):6615-21. Epub 2001 Nov 19. PMID:11714721
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