Systematic discovery of analogous enzymes in thiamin biosynthesis
| Autor: | Jan O. Korbel, Maricela Olvera, Enrique Morett, Gloria Saab-Rincón, Peer Bork, Leticia Olvera, Berend Snel, Steffen Schmidt, Emmanuvel Rajan |
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| Rok vydání: | 2003 |
| Předmět: |
Structural similarity
Molecular Sequence Data Hypothetical protein Biomedical Engineering Bioengineering Biology Models Biological Applied Microbiology and Biotechnology chemistry.chemical_compound Species Specificity Biosynthesis Sequence Analysis Protein Escherichia coli Animals Humans Amino Acid Sequence Thiamine Gene Sequence (medicine) chemistry.chemical_classification Alkyl and Aryl Transferases Sequence Homology Amino Acid food and beverages Isoenzymes Complementation Metabolic pathway Enzyme chemistry Biochemistry Molecular Medicine Energy Metabolism Cellular energy metabolism [UMCN 5.3] Sequence Alignment Biotechnology |
| Zdroj: | Nature Biotechnology, 21, pp. 790-795 Nature Biotechnology, 21, 790-795 |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | In all genome-sequencing projects completed to date, a considerable number of 'gaps' have been found in the biochemical pathways of the respective species. In many instances, missing enzymes are displaced by analogs, functionally equivalent proteins that have evolved independently and lack sequence and structural similarity. Here we fill such gaps by analyzing anticorrelating occurrences of genes across species. Our approach, applied to the thiamin biosynthesis pathway comprising approximately 15 catalytic steps, predicts seven instances in which known enzymes have been displaced by analogous proteins. So far we have verified four predictions by genetic complementation, including three proteins for which there was no previous experimental evidence of a role in the thiamin biosynthesis pathway. For one hypothetical protein, biochemical characterization confirmed the predicted thiamin phosphate synthase (ThiE) activity. The results demonstrate the ability of our computational approach to predict specific functions without taking into account sequence similarity. |
| Databáze: | OpenAIRE |
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