Document Detail

Neoglycopeptides as inhibitors of oligosaccharyl transferase: insight into negotiating product inhibition.
MedLine Citation:
PMID:  12498885     Owner:  NLM     Status:  MEDLINE    
Linear hexapeptides featuring the asparagine mimetics alanine-beta-hydrazide, alanine-beta-hydroxylamine, and 1,3-diaminobutanoic acid have been synthesized as oligosaccharyl transferase (OT) substrate mimetics and chemoselectively N-glycosylated to obtain the corresponding neoglycopeptides as OT product mimetics. The effect of glycosylation on the binding of these asparagine surrogates is in stark contrast with the effect of modification of native asparagine. In native N-linked glycosylation, product inhibition is minimal and glycopeptides show very low affinity for OT. In contrast, glycosylation of the substrate mimetics maintains or even improves affinity of the corresponding product mimetic for OT. Conformational considerations suggest that the flexibility of the N-glycosyl linkage in these neoglycopeptides allows them to be accommodated in the OT binding site while the native trans glycosyl amide linkage is rejected. These results provide insight into how OT minimizes product inhibition, thereby ensuring effective substrate turnover.
Stéphane Peluso; Maria de L Ufret; Mary K O'Reilly; Barbara Imperiali
Related Documents :
7737165 - Oligosaccharyl transferase is a constitutive component of an oligomeric protein complex...
2956995 - Glycosyltransfer by pea membranes from sugar nucleotides to added prenyl phosphates.
15652185 - Detection of glycosyltransferases in the golden hamster (mesocricetus auratus) oviduct ...
22575475 - Organelle growth control through limiting pools of cytoplasmic components.
11030425 - Iaa-synthase, an enzyme complex from arabidopsis thaliana catalyzing the formation of i...
25152065 - Molecular dynamics comparison of e. coli wrba apoprotein and holoprotein.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemistry & biology     Volume:  9     ISSN:  1074-5521     ISO Abbreviation:  Chem. Biol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-24     Completed Date:  2003-10-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9500160     Medline TA:  Chem Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1323-8     Citation Subset:  IM    
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Binding, Competitive
Carbohydrate Conformation
Glycopeptides / chemical synthesis*,  chemistry,  pharmacology*
Membrane Proteins*
Molecular Mimicry
Saccharomyces cerevisiae Proteins
Structure-Activity Relationship
Transferases / antagonists & inhibitors*
Grant Support
Reg. No./Substance:
0/Glycopeptides; 0/Membrane Proteins; 0/Saccharomyces cerevisiae Proteins; EC 2.-/Transferases; EC 2.4.1.-/Hexosyltransferases; EC - protein glycotransferase
Comment In:
Chem Biol. 2002 Dec;9(12):1266-8   [PMID:  12498877 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Sequence-dependent DNA dynamics by scanning force microscopy time-resolved imaging.
Next Document:  Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on a single cysteine ...