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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 10
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pubmed:dateCreated |
2005-10-5
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(N-morpholino)ethanesulfonic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Alkanesulfonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carbohydrates,
http://linkedlifedata.com/resource/pubmed/chemical/Cryoprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Galactose,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Glycopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Glycophorin,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/MNSs Blood-Group System,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0907-4449
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1386-94
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16204891-Alkanesulfonic Acids,
pubmed-meshheading:16204891-Antibodies,
pubmed-meshheading:16204891-Antigens,
pubmed-meshheading:16204891-Binding Sites,
pubmed-meshheading:16204891-Blood Proteins,
pubmed-meshheading:16204891-Carbohydrates,
pubmed-meshheading:16204891-Cryoprotective Agents,
pubmed-meshheading:16204891-Crystallography, X-Ray,
pubmed-meshheading:16204891-Electrons,
pubmed-meshheading:16204891-Galactose,
pubmed-meshheading:16204891-Glycerol,
pubmed-meshheading:16204891-Glycopeptides,
pubmed-meshheading:16204891-Glycophorin,
pubmed-meshheading:16204891-Glycosylation,
pubmed-meshheading:16204891-Humans,
pubmed-meshheading:16204891-Immunoglobulin Fab Fragments,
pubmed-meshheading:16204891-Immunoglobulin Fragments,
pubmed-meshheading:16204891-MNSs Blood-Group System,
pubmed-meshheading:16204891-Models, Chemical,
pubmed-meshheading:16204891-Models, Molecular,
pubmed-meshheading:16204891-Molecular Conformation,
pubmed-meshheading:16204891-Morpholines,
pubmed-meshheading:16204891-Mutation,
pubmed-meshheading:16204891-Protein Binding,
pubmed-meshheading:16204891-Protein Structure, Tertiary
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pubmed:year |
2005
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pubmed:articleTitle |
Crystallographic analysis of the NNA7 Fab and proposal for the mode of human blood-group recognition.
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pubmed:affiliation |
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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