High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in Human, Mouse, Rat, budding Yeast and E. coli.
High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in Human, Mouse, Rat, budding Yeast and E. coli.
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DOI：
10.1186/1471-2164-12-s3-s10
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发表时间：
2011-11-30
期刊：
影响因子：
4.4
通讯作者：
Qu H
中科院分区：
文献类型：
--
作者：
Zhao M;Qu H
系统发育图谱广泛用于表征没有氨基酸序列相似性的蛋白质之间的功能连接和保守性。为了调查不同物种代谢抑制网络中限速酶（RLE）的保守调节特性，我们将酶抑制对定义为：其中一对中的第一个酶是抑制剂提供者，第二个酶是抑制剂的目标。进一步生成抑制对中酶的系统发育谱，以测量这些酶在进化历史中的功能联系。我们发现，在每个被调查的模型生物体中，RLE 平均产生一半以上的体内抑制剂。这些抑制剂平均抑制代谢抑制网络中85%以上的靶点，覆盖了大部分跨通路抑制关系的靶点。此外，我们证明，至少一种酶具有限速作用的抑制对中的酶的系统发育谱通常比常见的抑制酶对表现出更高的相似性。此外，与常见的代谢酶相比，RLE 在保守的抑制网络中往往倾向于产生 ADP 而不是 AMP。结合 RLE 在感知代谢信号和向代谢系统其他部分传递调节信号的效率方面的保守作用，RLE 可能是通过维持活细胞中 ATP 与 ADP 的比率来平衡能量稳态的重要分子。此外，我们的结果表明，抑制酶对中酶的系统发育谱的相似性不仅与酶的拓扑重要性相关，而且与酶在代谢抑制网络中的作用相关。
The phylogenetic profile is widely used to characterize functional linkage and conservation between proteins without amino acid sequence similarity. To survey the conservative regulatory properties of rate-limiting enzymes (RLEs) in metabolic inhibitory network across different species, we define the enzyme inhibiting pair as: where the first enzyme in a pair is the inhibitor provider and the second is the target of the inhibitor. Phylogenetic profiles of enzymes in the inhibiting pairs are further generated to measure the functional linkage of these enzymes during evolutionary history. We find that the RLEs generate, on average, over half of all in vivo inhibitors in each surveyed model organism. And these inhibitors inhibit on average over 85% targets in metabolic inhibitory network and cover the majority of targets of cross-pathway inhibiting relations. Furthermore, we demonstrate that the phylogenetic profiles of the enzymes in inhibiting pairs in which at least one enzyme is rate-limiting often show higher similarities than those in common inhibiting enzyme pairs. In addition, RLEs, compared to common metabolic enzymes, often tend to produce ADP instead of AMP in conservative inhibitory networks. Combined with the conservative roles of RLEs in their efficiency in sensing metabolic signals and transmitting regulatory signals to the rest of the metabolic system, the RLEs may be important molecules in balancing energy homeostasis via maintaining the ratio of ATP to ADP in living cells. Furthermore, our results indicate that similarities of phylogenetic profiles of enzymes in the inhibiting enzyme pairs are not only correlated with enzyme topological importance, but also related with roles of the enzymes in metabolic inhibitory network.