2d03
From Proteopedia
(New page: 200px<br /> <applet load="2d03" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d03, resolution 1.97Å" /> '''Crystal structure o...) |
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| - | [[Image:2d03.gif|left|200px]]<br /> | + | [[Image:2d03.gif|left|200px]]<br /><applet load="2d03" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2d03, resolution 1.97Å" /> | caption="2d03, resolution 1.97Å" /> | ||
'''Crystal structure of the G91S mutant of the NNA7 Fab'''<br /> | '''Crystal structure of the G91S mutant of the NNA7 Fab'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The NNA7 Fab antibody fragment recognizes the human N-type blood-group | + | The NNA7 Fab antibody fragment recognizes the human N-type blood-group antigen comprised of the N-terminal glycopeptide of glycophorin A (GPA). A mutant form of this Fab fragment, NNA7-G91S, exhibits markedly reduced antigen binding. To provide insight into how these Fab fragments recognize this glycopeptide antigen, the crystal structures of NNA7 and NNA7-G91S were solved and refined to 1.83 and 1.97 A resolution, respectively. Both molecules are composed of the same heavy (H) chain Fd fragment, but each contains a slightly different light (L) chain owing to the G91S substitution. Specifically, the G91S mutation pushes the backbone of the neighboring H chain away from complementarity-determining region 3 (CDR3) of the L-chain variable region, allowing an additional glycerol cryoprotectant molecule to enter the antigen-combining site near the putative location of O-linked glycosylation. Each Fab fragment also possesses a well defined 2-(N-morpholino)ethanesulfonic acid (MES) molecule trapped in its antigen-combining site, as well as a crystallographic symmetry-related molecule comprising an amino-acid sequence that is virtually identical to the N-terminus of GPA. The MES molecule interacts with the H-chain CDR in a manner reminiscent of antibody-carbohydrate complexes. These results suggest a model for recognition of the glycopeptide antigen that accounts for the deleterious effect of the G91S substitution. |
==About this Structure== | ==About this Structure== | ||
| - | 2D03 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MES, GOL and PEG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2D03 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MES:'>MES</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=PEG:'>PEG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D03 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Song, S | + | [[Category: Song, S C.]] |
| - | [[Category: Spitalnik, S | + | [[Category: Spitalnik, S L.]] |
| - | [[Category: Wedekind, J | + | [[Category: Wedekind, J E.]] |
[[Category: Xie, K.]] | [[Category: Xie, K.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: antibody]] | [[Category: antibody]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:54:03 2008'' |
Revision as of 14:54, 21 February 2008
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Crystal structure of the G91S mutant of the NNA7 Fab
Overview
The NNA7 Fab antibody fragment recognizes the human N-type blood-group antigen comprised of the N-terminal glycopeptide of glycophorin A (GPA). A mutant form of this Fab fragment, NNA7-G91S, exhibits markedly reduced antigen binding. To provide insight into how these Fab fragments recognize this glycopeptide antigen, the crystal structures of NNA7 and NNA7-G91S were solved and refined to 1.83 and 1.97 A resolution, respectively. Both molecules are composed of the same heavy (H) chain Fd fragment, but each contains a slightly different light (L) chain owing to the G91S substitution. Specifically, the G91S mutation pushes the backbone of the neighboring H chain away from complementarity-determining region 3 (CDR3) of the L-chain variable region, allowing an additional glycerol cryoprotectant molecule to enter the antigen-combining site near the putative location of O-linked glycosylation. Each Fab fragment also possesses a well defined 2-(N-morpholino)ethanesulfonic acid (MES) molecule trapped in its antigen-combining site, as well as a crystallographic symmetry-related molecule comprising an amino-acid sequence that is virtually identical to the N-terminus of GPA. The MES molecule interacts with the H-chain CDR in a manner reminiscent of antibody-carbohydrate complexes. These results suggest a model for recognition of the glycopeptide antigen that accounts for the deleterious effect of the G91S substitution.
About this Structure
2D03 is a Single protein structure of sequence from Mus musculus with , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystallographic analysis of the NNA7 Fab and proposal for the mode of human blood-group recognition., Xie K, Song SC, Spitalnik SL, Wedekind JE, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1386-94. Epub 2005, Sep 28. PMID:16204891
Page seeded by OCA on Thu Feb 21 16:54:03 2008
Categories: Mus musculus | Single protein | Song, S C. | Spitalnik, S L. | Wedekind, J E. | Xie, K. | GOL | MES | PEG | Antibody
