Computational studies of the conformational landscape of allosteric and enantioselective enzymes
Enzymes are sophisticated biomacromolecules whose function is linked to its three-dimensional structure and conformational dynamics. Therefore, the understanding of enzyme conformational dynamics can be exploited to enhance enzyme efficiencies. First, we study alcohol dehydrogenase (ADH) enzymes in...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/671771 |
| Acceso en línea: | http://hdl.handle.net/10803/671771 |
| Access Level: | acceso abierto |
| Palabra clave: | Biocatalitzadors Biocatalizadores Biocatalysts Enzims Enzimas Enzymes Energia Energía Energy Al·losteria Alostería Allostery Dinàmica conformacional Dinámica conformacional Conformational dynamics Enantioselectivitat Enantioselectividad Enantioselectivity 544 577 |
| Sumario: | Enzymes are sophisticated biomacromolecules whose function is linked to its three-dimensional structure and conformational dynamics. Therefore, the understanding of enzyme conformational dynamics can be exploited to enhance enzyme efficiencies. First, we study alcohol dehydrogenase (ADH) enzymes in order to investigate the molecular basis of the reversion of enantioselectivity and thermo-adaptation displayed by laboratory-evolved enzyme variants towards non-natural substrates. In second place, we study the allosteric complex tryptophan synthase (TrpS) in order to decipher the allosteric effects exerted by the protein partner and by the introduction of mutations in laboratory evolved stand-alone enzyme variants. The study follows with the development of a strategy based on cross correlation tools in order to design stand-alone enzyme variants. Finally, the most promising computational designs are tested experimentally confirming their superior stand-alone activity. The studies gathered in this thesis emphasize the relevance of considering the enzyme conformational dynamics in computational enzyme engineering processes |
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