2d03
Crystal structure of the G91S mutant of the NNA7 Fab
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OverviewOverview
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 StructureAbout this Structure
2D03 is a Single protein structure of sequence from Mus musculus with MES, GOL and PEG as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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
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