Engineering a de Novo Transport Tunnel

Here we describe the computational design and directed evolution of a de novo transport tunnel in a haloalkane dehalogenase. Mutants with a blocked native tunnel and a newly opened auxiliary tunnel in a distinct part of the structure showed dramatically modified properties. The mutants with blocked tunnels acquired specificity never observed with native family members: up to 32 times increased substrate inhibition and 17 times reduced catalytic rates. Opening of the auxiliary tunnel resulted in specificity and substrate inhibition similar to those of the native enzyme and the most proficient haloalkane dehalogenase reported to date.

de_novo_tunnel

Brezovsky, J., Babkova, P., Degtjarik, O., Fortova, A., Gora, A., Iermak, I., Rezacova, P., Dvorak, P., Kuta Smatanova, I., Prokop, Z., Chaloupkova, R., Damborsky, J., 2016: Engineering a de Novo Transport Tunnel. ACS Catalysis 6: 7597-7610.

Open Postdoctoral Position: Protein Structural Biologist
Martin Marek’s Success in GAMU Project
Pleased to Announce a New Successful PhD Candidate: Tom Buryska
Congratulations to Piia and Colleagues on Their JACS Publication!
Woman Power Growing Stronger in LL: Lucinka
A New Addition to LL Team: Zanetka
Open Position: Laboratory Technician