Molecular analysis of the combining site of a monoclonal antibody against spermine
| Autor: | M. Le Roch, Nathalie Bouillé, Julie Johnston, Jacques Renault, Jacques-Philippe Moulinoux, Isabelle Debroise, Jean-Guy Delcros, Anne Royou |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Molecular Sequence Data Static Electricity Immunology Models Immunological Antibodies Monoclonal Spermine Mice Structure-Activity Relationship chemistry.chemical_compound Biochemistry chemistry Antibody Specificity Ionic strength Aspartic acid Animals Molecule Computer Simulation Paratope Amino Acid Sequence Tyrosine Binding site Polyamine Molecular Biology |
| Zdroj: | Molecular Immunology. 36:93-102 |
| ISSN: | 0161-5890 |
| Popis: | The structural basis of the binding of the polyamine spermine to the monoclonal antibody SPM8-2 was studied using computer modelling, ELISA methods and chemical modifications of the binding site residues. Paratope modelling showed that the antibody combining site forms a highly negatively charged cavity mainly shaped by aspartic acid and tyrosine residues which contact the tetra-positively charged spermine molecule by electrostatic interactions and hydrogen bondings. The importance of the electrostatic environment for spermine binding to SPM8-2 is emphasised by the strong dependency on pH and ionic strength. Specific chemical modifications of carboxylate groups and tyrosine residues of the antibody adsorbed to microtiter plates resulted in decreased binding of the N1-biotin-spermine conjugate used to monitor the activity of the antibody. These observations are consistent with a key role of aspartate and tyrosine residues in complex formation with spermine. These studies, important to our understanding of antibody-hapten specificity, may also shed light on important motifs responsible for protein-polyamine interactions. |
| Databáze: | OpenAIRE |
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