Identifying reaction modules in metabolic pathways: bioinformatic deduction and experimental validation of a new putative route in purine catabolism

BMC Systems Biology

Bernard Labedan³  Christianne Legrain¹  Raphaël Dutoit¹  Matthieu Barba² 

[1] Institut de Recherches Microbiologiques J.-M. Wiame IRMW, Campus CERIA, Av. E. Gryson 1, 1070, Brussels, Belgium;present address: Laboratoire de Biométrie et Biologie Évolutive, CNRS UMR 5558, Université Claude Bernard Lyon 1, 69622, Villeurbanne Cedex, France;present address: Bioinformatique, Laboratoire de Recherche en Informatique, CNRS UMR 8623, Université Paris Sud, Bâtiment 650, 91405, Orsay Cedex, France

关键词: Rubrobacter xylanophilus;    Functional annotation;    Reaction module;    Purine metabolism;    Pyrimidine metabolism;    Dihydroorotase dehydrogenase;    Cyclic amidohydrolases;    Dihydroorotase;   

Others  :  1142070
DOI  :  10.1186/1752-0509-7-99

 received in 2013-06-20, accepted in 2013-09-25,  发布年份 2013

【 摘 要 】

Background

Enzymes belonging to mechanistically diverse superfamilies often display similar catalytic mechanisms. We previously observed such an association in the case of the cyclic amidohydrolase superfamily whose members play a role in related steps of purine and pyrimidine metabolic pathways. To establish a possible link between enzyme homology and chemical similarity, we investigated further the neighbouring steps in the respective pathways.

Results

We identified that successive reactions of the purine and pyrimidine pathways display similar chemistry. These mechanistically-related reactions are often catalyzed by homologous enzymes. Detection of series of similar catalysis made by succeeding enzyme families suggested some modularity in the architecture of the central metabolism. Accordingly, we introduce the concept of a reaction module to define at least two successive steps catalyzed by homologous enzymes in pathways alignable by similar chemical reactions. Applying such a concept allowed us to propose new function for misannotated paralogues. In particular, we discovered a putative ureidoglycine carbamoyltransferase (UGTCase) activity. Finally, we present experimental data supporting the conclusion that this UGTCase is likely to be involved in a new route in purine catabolism.

Conclusions

Using the reaction module concept should be of great value. It will help us to trace how the primordial promiscuous enzymes were assembled progressively in functional modules, as the present pathways diverged from ancestral pathways to give birth to the present-day mechanistically diversified superfamilies. In addition, the concept allows the determination of the actual function of misannotated proteins.

【 授权许可】

   
2013 Barba et al.; licensee BioMed Central Ltd.

【 图 表 】

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