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


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 approximately 1 kcal mol-1 as monitored by thermal denaturation. Study holds ProTherm entries: 9373 Extra Details: threonine-linked L-fucose moiety; simulated annealing; hydrophobic and hydrogen bond interactions; fucosylated inhibitor; exchange rates of amide protons; dynamic fluctuations

Submission Details

ID: 5HjRX9z73

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:37 p.m.

Version: 1

Publication Details
Mer G;Hietter H;Lefèvre JF,Nat. Struct. Biol. (1996) Stabilization of proteins by glycosylation examined by NMR analysis of a fucosylated proteinase inhibitor. PMID:8548454
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