6C7M
Directed evolutionary changes in Kemp Eliminase KE07 - Crystal 19 round 5
Summary for 6C7M
| Entry DOI | 10.2210/pdb6c7m/pdb |
| Descriptor | Kemp Eliminase KE07, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total) |
| Functional Keywords | kemp eliminase, directed evolution, ke07, de novo protein, lyase |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 29683.07 |
| Authors | Jackson, C.J.,Hong, N.-S.,Carr, P.D. (deposition date: 2018-01-22, release date: 2018-08-01, Last modification date: 2023-10-04) |
| Primary citation | 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 Cited by 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: 30254369DOI: 10.1038/s41467-018-06305-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
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