期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：25
页码：15023-15028
DOI：10.1073/pnas.2431286100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The structure of a complex between the Fab fragment of the antibody (SYA/J6) specific for the cell surface O-antigen polysaccharide of the pathogen Shigella flexneri Y and an octapeptide (Met-Asp-Trp-Asn-Met-His-Ala-Ala), a functional mimic of the O-antigen, has been determined at 1.8-A resolution. Comparison of the structure with that of the complex with the pentasaccharide antigen [[->]2)--L-Rha-(1[->]2)--L-Rha-(1[->]3)--L-Rha-(1[->]3)-{beta}-D-GlcNAc-(1[->]2)--L-Rha-(1[->]] reveals the molecular recognition process by which a peptide mimics a carbohydrate in binding to an antibody. The binding modes of the two ligands differ considerably. Octapeptide binding complements the shape of the combining site groove much better than pentasaccharide binding. Moreover, the peptide makes a much greater number of contacts (126), which are mostly van der Waals interactions, with the Fab than the saccharide (74). An unusual feature is also the involvement of 12 water molecules in mediating hydrogen bonds between residues within the peptide or of the peptide and Fab. Despite better shape complementarity and greater number of contacts, the octapeptide binds with an affinity (KA = 2.5 x 105 M-1, measured by calorimetry) only {approx}2-fold tighter than the pentasaccharide. The structural results are relevant to the design of peptide mimetics with improved affinity for use as vaccines.
