{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:22:28Z","timestamp":1791278548979,"version":"4.1.0"},"reference-count":40,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>Three mutations of the B4GALT7 gene [encoding \u03b21,4-GalT7 (\u03b21,4-galactosyltransferase 7)], corresponding to A186D, L206P and R270C, have been identified in patients with the progeroid form of the Ehlers\u2013Danlos syndrome and are described as being associated with the reduction or loss of \u03b21,4-GalT7 activity. However, the molecular basis of the reduction or loss of activity remained to be determined. In the present study, wild-type, A186D, L206P and R270C \u03b21,4-GalT7 were expressed in CHO618 cells as membrane proteins and in Escherichia coli as soluble proteins fused to MBP (maltose-binding protein). The ability of the expressed proteins to transfer galactose from donor to acceptor substrates was systematically characterized by kinetic analysis. The physicochemical properties of soluble proteins were explored by isothermal titration calorimetry, which is a method of choice when determining the thermodynamic parameters of the binding of substrates. Together, the results showed that: (i) the L206P mutation abolished the activity when L206P \u03b21,4GalT7 was either inserted in the membrane or expressed as a soluble MBP\u2013full-length fusion protein; (ii) the A186D mutation weakly impaired the binding of the donor substrate; and (iii) the R270C mutation strongly impaired the binding of the acceptor substrate. Moreover, the ex vivo consequences of the mutations were investigated by evaluating the priming efficiency of xylosides on GAG (glycosaminoglycan) chain initiation. The results demonstrate a quantitative effect on GAG biosynthesis, depending on the mutation; GAG biosynthesis was fully inhibited by the L206P mutation and decreased by the R270C mutation, whereas the A186D mutation did not affect GAG biosynthesis severely.<\/jats:p>","DOI":"10.1042\/bj20100921","type":"journal-article","created":{"date-parts":[[2010,9,2]],"date-time":"2010-09-02T13:20:15Z","timestamp":1283433615000},"page":"303-311","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Biochemical and thermodynamic characterization of mutated \u03b21,4-galactosyltransferase 7 involved in the progeroid form of the Ehlers\u2013Danlos syndrome"],"prefix":"10.1042","volume":"432","author":[{"given":"Sophie","family":"Rahuel-Clermont","sequence":"first","affiliation":[{"name":"ARN-RNP-structure fonction-maturation, Enzymologie Mol\u00e9culaire et Structurale, Unit\u00e9 Mixte de Recherche 7214, CNRS-Nancy Universit\u00e9, Facult\u00e9 des Sciences et Techniques, BP 239 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Daligault","sequence":"additional","affiliation":[{"name":"Physiopathologie, Pharmacologie et Ing\u00e9nierie Articulaires, Unit\u00e9 Mixte de Recherche 7561, CNRS-Nancy Universit\u00e9, Facult\u00e9 de M\u00e9decine, BP 184 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Helene","family":"Piet","sequence":"additional","affiliation":[{"name":"Physiopathologie, Pharmacologie et Ing\u00e9nierie Articulaires, Unit\u00e9 Mixte de Recherche 7561, CNRS-Nancy Universit\u00e9, Facult\u00e9 de M\u00e9decine, BP 184 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Gulberti","sequence":"additional","affiliation":[{"name":"Physiopathologie, Pharmacologie et Ing\u00e9nierie Articulaires, Unit\u00e9 Mixte de Recherche 7561, CNRS-Nancy Universit\u00e9, Facult\u00e9 de M\u00e9decine, BP 184 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Netter","sequence":"additional","affiliation":[{"name":"Physiopathologie, Pharmacologie et Ing\u00e9nierie Articulaires, Unit\u00e9 Mixte de Recherche 7561, CNRS-Nancy Universit\u00e9, Facult\u00e9 de M\u00e9decine, BP 184 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Branlant","sequence":"additional","affiliation":[{"name":"ARN-RNP-structure fonction-maturation, Enzymologie Mol\u00e9culaire et Structurale, Unit\u00e9 Mixte de Recherche 7214, CNRS-Nancy Universit\u00e9, Facult\u00e9 des Sciences et Techniques, BP 239 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Magdalou","sequence":"additional","affiliation":[{"name":"Physiopathologie, Pharmacologie et Ing\u00e9nierie Articulaires, Unit\u00e9 Mixte de Recherche 7561, CNRS-Nancy Universit\u00e9, Facult\u00e9 de M\u00e9decine, BP 184 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Lattard","sequence":"additional","affiliation":[{"name":"Physiopathologie, Pharmacologie et Ing\u00e9nierie Articulaires, Unit\u00e9 Mixte de Recherche 7561, CNRS-Nancy Universit\u00e9, Facult\u00e9 de M\u00e9decine, BP 184 Vandoeuvre-Les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,11,12]]},"reference":[{"key":"2021112217342140600_B1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O","article-title":"Ehlers\u2013Danlos syndromes: revised nosology, Villefranche, 1997. 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