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

被引：32

作者：

Esposito, G

Vitagliano, L

Santamaria, R

Viola, A

Zagari, A

Salvatore, F

机构：

[1] Univ Naples Federico II, CEINGE Biotecnol Avanzate, Dipartimento Biochim & Biotecnol Med, I-80131 Naples, Italy

[2] Univ Naples Federico II, CNR, Ist Biostrutture & Bioimmagini, I-80134 Naples, Italy

[3] Univ Naples Federico II, Dipartimento Chim Biol, I-80134 Naples, Italy

来源：

FEBS LETTERS | 2002年 / 531卷 / 02期

关键词：

aldolase B; hereditary fructose intolerance; site-directed mutagenesis; protein expression; kinetic analysis; homology-modeling technique;

D O I：

10.1016/S0014-5793(02)03451-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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 BEL (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：152 / 156

页数：5

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