title: Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance.
abstract: Hereditary fructose intolerance (HFI) is a recessively inherited disorder of carbohydrate metabolism caused by impaired function of human liver aldolase (B isoform). 25 enzyme-impairing mutations have been identified in the aldolase B gene. We have studied the HFI-related mutant recombinant proteins W147R, A149P, A174D, L256P, N334K and delta6ex6 in relation to aldolase B function and structure using kinetic assays and molecular graphics analysis. We found that these mutations affect aldolase B function by decreasing substrate affinity, maximal velocity and/or enzyme stability. Finally, the functional and structural analyses of the non-natural mutant Q354E provide insight into the catalytic role of Arg(303), whose natural mutants are associated to HFI.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Esposito
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.forename: Rita
authors.initials: R
authors.lastname: Santamaria
authors.forename: Antonietta
authors.initials: A
authors.lastname: Viola
authors.forename: Adriana
authors.initials: A
authors.lastname: Zagari
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
mesh_terms: D001120:Arginine / Q000502:physiology; D002384:Catalysis; D005633:Fructose Intolerance / Q000235:genetics; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011994:Recombinant Proteins; D001120:Arginine; D005634:Fructose-Bisphosphate Aldolase