Sequence-function-stability relationships in proteins from datasets of functionally annotated variants: the case of TEM β-lactamases.
| Autor: | Abriata LA; Instituto de Biología Molecular y Celular de Rosario, Rosario, Argentina. luciano.abriata@epfl.ch, Salverda ML, Tomatis PE |
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| Jazyk: | angličtina |
| Zdroj: | FEBS letters [FEBS Lett] 2012 Sep 21; Vol. 586 (19), pp. 3330-5. Date of Electronic Publication: 2012 Jul 28. |
| DOI: | 10.1016/j.febslet.2012.07.010 |
| Abstrakt: | A dataset of TEM lactamase variants with different substrate and inhibition profiles was compiled and analyzed. Trends show that loops are the main evolvable regions in these enzymes, gradually accumulating mutations to generate increasingly complex functions. Notably, many mutations present in evolved enzymes are also found in simpler variants, probably originating functional promiscuity. Following a function-stability tradeoff, the increase in functional complexity driven by accumulation of mutations fosters the incorporation of other stability-restoring substitutions, although our analysis suggests they might not be as "global" as generally accepted and seem instead specific to different networks of protein sites. Finally, we show how this dataset can be used to model functional changes in TEMs based on the physicochemical properties of the amino acids. (Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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