TY - JOUR
T1 - Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance
AU - Esposito, Gabriella
AU - Vitagliano, Luigi
AU - Santamaria, Rita
AU - Viola, Antonietta
AU - Zagari, Adriana
AU - Salvatore, Francesco
PY - 2002/11/6
Y1 - 2002/11/6
N2 - 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.
AB - 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.
KW - Aldolase B
KW - Hereditary fructose intolerance
KW - Homology-modeling technique
KW - Kinetic analysis
KW - Protein expression
KW - Site-directed mutagenesis
UR - http://www.scopus.com/inward/record.url?scp=0037032455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037032455&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(02)03451-8
DO - 10.1016/S0014-5793(02)03451-8
M3 - Article
C2 - 12417303
AN - SCOPUS:0037032455
SN - 0014-5793
VL - 531
SP - 152
EP - 156
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -