Molecular Recognition of beta-O-GlcNAc Glycopeptides by a Lectin-Like Receptor: Binding Modulation by the Underlying Ser or Thr Amino Acids

  1. Corzana, F. 2
  2. Fernández-Tejada, A. 2
  3. Busto, J.H. 2
  4. Joshi, G. 3
  5. Davis, A.P. 3
  6. Jiménez-Barbero, J. 1
  7. Avenoza, A. 2
  8. Peregrina, J.M. 2
  1. 1 Centro de Investigaciones Biológicas
    info

    Centro de Investigaciones Biológicas

    Madrid, España

    ROR https://ror.org/04advdf21

  2. 2 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  3. 3 University of Bristol
    info

    University of Bristol

    Brístol, Reino Unido

    ROR https://ror.org/0524sp257

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Revista:
Chembiochem : a European journal of chemical biology

ISSN: 1439-4227

Año de publicación: 2011

Volumen: 12

Número: 1

Páginas: 110-117

Tipo: Artículo

beta Ver similares en nube de resultados
DOI: 10.1002/CBIC.201000526 PMID: 21181845 SCOPUS: 2-s2.0-78650710694 WoS: WOS:000285771200013 GOOGLE SCHOLAR

Otras publicaciones en: Chembiochem : a European journal of chemical biology

Objetivos de desarrollo sostenible

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Resumen

The binding properties of different carbohydrates and glycopeptides containing the β-O-2-deoxy-2-(N-acetyl)-D-glucosaminyl (β-O-GlcNAc) to a synthetically prepared lectin-like receptor have been analyzed. The study combines the use of NMR spectroscopy experiments with extensive MD simulations in explicit water. Notably, the presence of a key hydrogen bond between the receptor and the OMe group of the β-O-GlcNAc-OMe derivative appears to be responsible for the high selectivity observed for this compound. In addition, to study the effect on the binding of the underlying amino acid, we have prepared different model glycopeptides, which include the non-natural α-methylserine and α-methylthreonine as underlying amino acids. Interestingly, the presence of a methyl group decreases the affinity constant, especially in those cases in which a β-methyl group is present. As a result, the serine-containing glycopeptide exhibited the highest affinity constant of the glycopeptides, and the threonine derivative showed the lowest one. This low selectivity could have its origin in the difficulty to form both specific hydrogen bonds and hydrophobic (CH-π) contacts.The binding properties of different carbohydrates and glycopeptides with β-O-GlcNAc to a synthetically prepared lectin-like receptor have been analyzed. A serine-containing glycopeptide exhibited the highest affinity constant of the glycopeptides, and a threonine derivative showed the lowest one. This low selectivity could have its origin in the difficulty to form both specific hydrogen bonds and hydrophobic (CH-π) contacts. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.