Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance

Gabriella Esposito, Luigi Vitagliano, Rita Santamaria, Antonietta Viola, Adriana Zagari, Francesco Salvatore

Research output: Contribution to journalArticle

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 Δ6ex6 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 Arg303, whose natural mutants are associated to HFI.

Original languageEnglish
Pages (from-to)152-156
Number of pages5
JournalFEBS Letters
Volume531
Issue number2
DOIs
Publication statusPublished - Nov 6 2002

Keywords

  • Aldolase B
  • Hereditary fructose intolerance
  • Homology-modeling technique
  • Kinetic analysis
  • Protein expression
  • Site-directed mutagenesis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Esposito, G., Vitagliano, L., Santamaria, R., Viola, A., Zagari, A., & Salvatore, F. (2002). Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance. FEBS Letters, 531(2), 152-156. https://doi.org/10.1016/S0014-5793(02)03451-8