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Stabilization of proteins by glycosylation examined by NMR analysis of a fucosylated proteinase inhibitor

Nature Structural Biology volume 3, pages 45–53 (1996)Cite this article

An Erratum to this article was published on 01 March 1996

Abstract

Here we investigate the effects of the naturally occuring threonine-linked L-fucose moiety on the structure, dynamics and stability of the proteinase inhibitor PMP-C (Pars intercerebralis major peptide C). The three-dimensional structure of PMP-C fucosylated on Thr 9 has been determined by NMR spectroscopy and simulated annealing. The f ucose ring is very well ordered, held in place by hydrophobic and hydrogen bond interactions with Thr 16 and Arg 18. Comparing the NMR data and the structure of the fucosylated inhibitor with those of the nonf ucosylated form shows that conformational changes only occur in the vicinity of the fucose moiety. Nevertheless, a comparative analysis of the exchange rates of amide protons indicates that fucosylation is responsible for an overall decrease of the dynamic fluctuations of the molecule. This correlates well with an increase in stability of ∼1 kcal mol−1 as monitored by thermal denaturation.

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Authors and Affiliations

  1. CNRS–UPR 9003, Ecole Supérieure de Biotechnologie de Strasbourg, Bd Sébastien Brant, 67400, Illkirch-Graffenstaden, France

    Georges Mer & Jean-François Lefèvre

  2. Laboratoire de chimie organique des substances naturelles, Université Louis Pasteur, CNRS–URA 31,5, rue Blaise Pascal, 67084, Strasbourg, France

    Hélène Hietter

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  1. Georges Mer
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Mer, G., Hietter, H. & Lefèvre, JF. Stabilization of proteins by glycosylation examined by NMR analysis of a fucosylated proteinase inhibitor. Nat Struct Mol Biol 3, 45–53 (1996). https://doi.org/10.1038/nsb0196-45

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