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

Lookup NU author(s): Dr Catherine Bui

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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. © 2010 Federation of European Biochemical Societies.

Publication metadata

Author(s): Bui C, Talhaoui I, Chabel M, Mulliert G, Coughtrie M, Ouzzine M, Fournel-Gigleux S

Publication type: Article

Publication status: Published

Journal: FEBS Letters

Year: 2010

Volume: 584

Issue: 18

Pages: 3962-3968

Print publication date: 05/08/2010

ISSN (print): 0014-5793

ISSN (electronic): 1873-3468

Publisher: Elsevier BV

URL: http://dx.doi.org/10.1016/j.febslet.2010.08.001

DOI: 10.1016/j.febslet.2010.08.001

PubMed id: 20691685

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