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

Georges Mer, Hélène Hietter, Jean François Lefèvre

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Here we investigate the effects of the naturally occurring 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 fucose 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 nonfucosylated 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.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalNature Structural Biology
Volume3
Issue number1
DOIs
StatePublished - Jan 25 1996

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

Fingerprint Dive into the research topics of 'Stabilization of proteins by glycosylation examined by NMR analysis of a fucosylated proteinase inhibitor'. Together they form a unique fingerprint.

  • Cite this