Symmetry-related residues as promising hotspots for the evolution of de novo oligomeric enzymes
| العنوان: | Symmetry-related residues as promising hotspots for the evolution of de novo oligomeric enzymes |
|---|---|
| المؤلفون: | Chaok Seok, Jinsol Yang, Woon Ju Song, Jaeseung Yu |
| المصدر: | Chemical Science. 12:5091-5101 |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | chemistry.chemical_classification, 0303 health sciences, biology, High-throughput screening, Active site, General Chemistry, Computational biology, Global symmetry, 010402 general chemistry, Directed evolution, 01 natural sciences, 0104 chemical sciences, 03 medical and health sciences, Enzyme, chemistry, biology.protein, Symmetry (geometry), 030304 developmental biology |
| الوصف: | Directed evolution has provided us with great opportunities and prospects in the synthesis of tailor-made proteins. It, however, often requires at least mid to high throughput screening, necessitating more effective strategies for laboratory evolution. We herein demonstrate that protein symmetry can be a versatile criterion for searching for promising hotspots for the directed evolution of de novo oligomeric enzymes. The randomization of symmetry-related residues located at the rotational axes of artificial metallo-β-lactamase yields drastic effects on catalytic activities, whereas that of non-symmetry-related, yet, proximal residues to the active site results in negligible perturbations. Structural and biochemical analysis of the positive hits indicates that seemingly trivial mutations at symmetry-related spots yield significant alterations in overall structures, metal-coordination geometry, and chemical environments of active sites. Our work implicates that numerous artificially designed and natural oligomeric proteins might have evolutionary advantages of propagating beneficial mutations using their global symmetry. |
| تدمد: | 2041-6539 2041-6520 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::839d4cba6fb92b3ab6c6e3f27ee791c4 https://doi.org/10.1039/d0sc06823c |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........839d4cba6fb92b3ab6c6e3f27ee791c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20416539 20416520 |
|---|