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High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in human, mouse, rat, budding yeast and E. coli
Journal article   Open access   Peer reviewed

High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in human, mouse, rat, budding yeast and E. coli

Min Zhao and H Qu
BMC Genomics, Vol.12(Supplement 3), p.S10
10th International Conference on Bioinformatics (InCoB) and 1st ISCB-Asia Joint Conference: Computational Biology, 2011 (Kuala Lumpur, Malaysia, 30-Nov-2011–02-Dec-2011)
2011
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https://doi.org/10.1186/1471-2164-12-S3-S10View
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Abstract

amino acid sequence balancing energy E. coli evolutionary history in-vivo living cell metabolic enzymes metabolic signals metabolic systems model organisms phylogenetic profile rate limiting rate-limiting enzymes regulatory properties
Background: 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. Results: 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. Conclusions: 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. © 2011 licensee BioMed Central Ltd.

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