The glycosomal ATP-dependent phosphofructokinase of Trypanosoma brucei must have evolved from an ancestral pyrophosphate-dependent enzyme.

The glycosomal ATP-dependent phosphofructokinase of Trypanosoma brucei must have evolved from an ancestral pyrophosphate-dependent enzyme.
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布氏锥虫的糖体 ATP 依赖性磷酸果糖激酶必定是从祖先的焦磷酸依赖性酶进化而来。

DOI:
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发表时间:
1997
期刊:
European Journal of Biochemistry
影响因子:
--
通讯作者:
D. J. Rigden
D. J. Rigden
中科院分区:
--
文献类型:
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作者:
P. Michels;N. Chevalier;F. Opperdoes;Mark H. Rider;D. J. Rigden

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布氏锥虫含有ATP依赖性磷酸果糖激酶(PFK),位于其糖体中,糖体是过氧化物酶体样细胞器,隔离其大部分糖酵解酶。在本文中,我们报告的单拷贝基因编码这种酶的克隆和测序。其氨基酸序列与焦磷酸盐(PPi)依赖性PFKs比其他ATP依赖性PFKs更相似。系统发育分析表明,该酶必须已经从一个PPi依赖的祖先PFK,这改变了其磷酸供体特异性在进化过程中。该酶不再能够使用PPi作为磷酸底物,也不能像PPi-PFK通常那样催化逆反应。此外,细胞中存在高焦磷酸酶活性使得PPi不太可能在当今锥虫中充当自由能源。仍有待确定哪些突变是导致锥虫PFK磷酸化底物特异性改变的原因。由于其独特的进化历史,T.与其他ATP依赖性PFK相比,布氏PFK显示出许多结构差异,甚至在活性位点。这些差异为基于结构的杀锥虫药物设计提供了巨大的潜力。
Trypanosoma brucei contains an ATP-dependent phosphofructokinase (PFK), located in its glycosomes, which are peroxisome-like organelles sequestering the majority of its glycolytic enzymes. In this paper, we report the cloning and sequencing of the single-copy gene encoding this enzyme. Its amino-acid sequence is more similar to pyrophosphate (PPi)-dependent PFKs than to other ATP-dependent PFKs. A phylogenetic analysis suggests that the enzyme must have been derived from a PPi-dependent ancestral PFK, which changed its phospho-donor specificity during evolution. The enzyme is no longer capable of using PPi as phospho substrate, nor can it catalyze the reverse reaction as PPi-PFKs generally can. Moreover, the presence of a high pyrophosphatase activity in the cell renders it unlikely that PPi can function as free-energy source in present-day trypanosomes. It remains to be determined which mutations were responsible for the change in phospho-substrate specificity of the trypanosomatid PFK. As a result of its particular evolutionary history, the T. brucei PFK shows many structural differences, even at the active site, when compared with other ATP-dependent PFKs. These differences offer great potential for the structure-based design of trypanocidal drugs.
DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
作者:
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DOI: 10.1091/mbc.3.7.749
发表时间: 1992
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