Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
FEBS Lett. 2010 Sep 24;584(18):3962-8. doi: 10.1016/j.febslet.2010.08.001. Epub 2010 Aug 6.

Molecular characterization of β1,4-galactosyltransferase 7 genetic mutations linked to the progeroid form of Ehlers-Danlos syndrome (EDS).

Author information

  • 1UMR 7561 CNRS-Université de Nancy I, Faculté de Médecine, Vandoeuvre-lès-Nancy, France.

Abstract

β1,4-Galactosyltransferase 7 (β4GalT7) is a key enzyme initiating glycosaminoglycan (GAG) synthesis. Based on in vitro and ex vivo kinetics studies and structure-based modelling, we molecularly characterized β4GalT7 mutants linked to the progeroid form of Ehlers-Danlos syndrome (EDS), a severe connective tissue disorder. Our results revealed that loss of activity upon L206P substitution due to altered protein folding is the primary cause for the GAG synthesis defect in patients carrying the compound A186D and L206P mutations. We showed that R270C substitution strongly reduced β4GalT7 affinity towards xyloside acceptor, thus affecting GAG chains formation. This study establishes the molecular basis for β4GalT7 defects associated with altered GAG synthesis in EDS.

Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PMID:
20691685
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk