Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance
Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance
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DOI：
10.1016/s0014-5793(02)03451-8
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发表时间：
2002-11-06
期刊：
影响因子：
3.5
通讯作者：
Salvatore, F
中科院分区：
文献类型：
--
作者：
Esposito, G;Vitagliano, L;Salvatore, F
遗传性果糖不耐症（HFI）是一种由肝脏醛缩酶（B亚型）功能受损引起的糖代谢障碍性疾病。在醛缩酶B基因中已鉴定出25种酶损伤突变。我们利用动力学分析和分子图形学分析研究了HFI相关突变重组蛋白W147 R、A149 P、A174 D、L256 P、N334 K和Delta 6 ex 6与醛缩酶B功能和结构的关系。我们发现这些突变通过降低底物亲和力、最大速度和/或酶稳定性来影响醛缩酶B的功能。最后，非天然突变体Q354 E的功能和结构分析提供了对Arg（303）的催化作用的深入了解，其天然突变体与BEL（C）2002欧洲生物化学学会联合会有关。由Elsevier Science B. V.出版，版权所有。
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.