title: Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency.
abstract: Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin-dependent carboxylases found in humans. A deficiency in HCS results in biotin-responsive multiple carboxylase deficiency (MCD). We have identified six different point mutations in the HCS gene in nine patients with MCD. Two of the mutations are frequent among the MCD patients analyzed. Four of the mutations cluster in the putative biotin-binding domain as deduced from the corresponding Escherichia coli enzyme and consistent with an explanation for biotin-responsiveness based on altered affinity for biotin. The two others may define an additional domain involved in biotin-binding or biotin-mediated stabilization of the protein.
authors.affiliation: McGill University, Department of Biology, Montreal Children's Hospital Research Institute, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Dupuis
authors.forename: A
authors.initials: A
authors.lastname: Leon-Del-Rio
authors.forename: D
authors.initials: D
authors.lastname: Leclerc
authors.forename: E
authors.initials: E
authors.lastname: Campeau
authors.forename: L
authors.initials: L
authors.lastname: Sweetman
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: G
authors.initials: G
authors.lastname: Herman
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
authors.forename: R A
authors.initials: RA
authors.lastname: Gravel
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001710:Biotin / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases; D002460:Cell Line; D005347:Fibroblasts; D006801:Humans; D007231:Infant, Newborn; D008025:Ligases / Q000235:genetics*; D008969:Molecular Sequence Data; D009100:Multiple Carboxylase Deficiency / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D001710:Biotin; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases