6C7V

Directed evolutionary changes in Kemp Eliminase KE07 - Crystal 22 round 5

6C7V の概要

• エントリーDOI: 10.2210/pdb6c7v/pdb
• 分子名称: Kemp eliminase KE07 (2 entities in total)
• 機能のキーワード: kemp eliminase, directed evolution, ke07, de novo protein, lyase
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27943.07

構造登録者

Jackson, C.J.,Hong, N.-S.,Carr, P.D. (登録日: 2018-01-23, 公開日: 2018-08-01, 最終更新日: 2023-10-04)

主引用文献

Hong, N.S.,Petrovic, D.,Lee, R.,Gryn'ova, G.,Purg, M.,Saunders, J.,Bauer, P.,Carr, P.D.,Lin, C.Y.,Mabbitt, P.D.,Zhang, W.,Altamore, T.,Easton, C.,Coote, M.L.,Kamerlin, S.C.L.,Jackson, C.J.
The evolution of multiple active site configurations in a designed enzyme.
Nat Commun, 9:3900-3900, 2018

PubMed Abstract: Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.

PubMed: 30254369
DOI: 10.1038/s41467-018-06305-y

実験手法

X-RAY DIFFRACTION (1.64 Å)