Composition of Drosophila melanogaster proteome involved in fucosylated glyean metabolism

Composition of Drosophila melanogaster proteome involved in fucosylated glyean metabolism
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DOI:
10.1074/jbc.m107927200
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发表时间:
2002-02-01
影响因子:
4.8
通讯作者:
Renkonen, R
Renkonen, R
中科院分区:
生物学2区
文献类型:
--
作者:
Roos, C;Kolmer, M;Renkonen, R

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全基因组方法能够表征任何给定生物途径的所有成分。此外,它可以帮助揭示任何分子的所有代谢途径。在这里,我们利用黑腹果蝇的基因组来寻找参与浓缩聚糖代谢的酶。我们的研究结果表明,在果蝇中,聚焦转移酶反应的供体GDP- focus完全通过GDP-甘露糖通过GDP- d -甘露糖4,6-脱水酶(GMD)和GDP-4-酮-6-脱氧-d -甘露糖3,5-烯丙基酶/4-还原酶(GMER,在人类中也称为FX)催化的酶促反应通过从头途径形成。果蝇基因组中没有与救助途径酶同源的酶,即岩藻激酶和GDP- focus焦磷酸化酶,它们从focus合成GDP- focus。此外,我们还发现了两种新的聚焦转移酶,预测它们可以催化α 1,3和α 1,6与糖聚糖上的GlcNAc残基的特异性连接。没有发现编码alpha1,2特异性聚焦转移酶的基因。我们还在果蝇基因组中发现了两个编码O-聚焦转移酶的新基因和一个负责聚焦酶的基因。最后,利用果蝇CG4435基因,我们鉴定了两个新的人类基因,推测编码聚焦基转移酶。这项工作可以作为进一步绘制所有可能的糖基化途径的全基因组方法的基础,并作为后续实验研究的基础分析,以验证本工作中的预测。
The whole genome approach enables the characterization of all components of any given biological pathway. Moreover, it can help to uncover all the metabolic routes for any molecule. Here we have used the genome of Drosophila melanogaster to search for enzymes involved in the metabolism of fucosylated glycans. Our results suggest that in the fruit fly GDP-fucose, the donor for fucosyltransferase reactions, is formed exclusively via the de novo pathway from GDP-mannose through enzymatic reactions catalyzed by GDP-D-mannose 4,6-dehydratase(GMD) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (GMER, also known as FX in man). The Drosophila genome does not have orthologs for the salvage pathway enzymes, i.e. fucokinase and GDP-fucose pyrophosphorylase synthesizing GDP-fucose from fucose. In addition we identified two novel fucosyltransferases predicted to catalyze alpha1,3-and alpha1,6-specific linkages to the GlcNAc residues on glycans. No genes with the capacity to encode alpha1,2-specific fucosyltransferases were found. We also identified two novel genes coding for O-fucosyltransferases and a gene responsible for a fucosidase enzyme in the Drosophila genome. Finally, using the Drosophila CG4435 gene, we identified two novel human genes putatively coding for fucosyltransferases. This work can serve as a basis for further whole-genome approaches in mapping all possible glycosylation pathways and as a basic analysis leading to subsequent experimental studies to verify the predictions made in this work.