Abstract
Mutational events as well as the selection of the optimal variant are essential steps in the evolution of living organisms. The same principle is used in laboratory to extend the natural biodiversity to obtain better catalysts for applications in biomanufacturing or for improved biopharmaceuticals. Furthermore, single mutation in genes of drug-metabolizing enzymes can also result in dramatic changes in pharmacokinetics. These changes are a major cause of patient-specific drug responses and are, therefore, the molecular basis for personalized medicine. MuteinDB systematically links laboratory-generated enzyme variants (muteins) and natural isoforms with their biochemical properties including kinetic data of catalyzed reactions. Detailed information about kinetic characteristics of muteins is available in a systematic way and searchable for known mutations and catalyzed reactions as well as their substrates and known products. MuteinDB is broadly applicable to any known protein and their variants and makes mutagenesis and biochemical data searchable and comparable in a simple and easy-to-use manner. For the import of new mutein data, a simple, standardized, spreadsheet-based data format has been defined. To demonstrate the broad applicability of the MuteinDB, first data sets have been incorporated for selected cytochrome P450 enzymes as well as for nitrilases and peroxidases.Database URL: http://www.MuteinDB.org
Highlights
One of nature’s fundamental mechanisms to create genetic diversity in living organisms is the creation of mutants, which, in turn, leads to evolution
Physicians recognized that patients with the same disease responded differently to drugs, according to which allelic variant their genomes were carrying
Muteins generated either by rational design or by directed or designed evolution were adapted to the needs of industrial processes or for completely new applications
Summary
One of nature’s fundamental mechanisms to create genetic diversity in living organisms is the creation of mutants, which, in turn, leads to evolution. None of these databases provides kinetic characteristics of muteins and allows a fast, systematic and user-friendly way to search for known mutations and catalyzed reactions of interest. None of the existing databases is searchable by substrate or product molecule structures allowing comparison of muteins with respect to their catalytic properties.
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