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.

New addition to Loschmidt Laboratories team
Submitted grant proposal to Bill Gates Foundation
FireProt 1.0 released and accompanied by a publication
David Pluskal awarded Grammar School Student Award of The Learned Society of the Czech Republic
Klara Markova to attend Summer School ‘Exploring Natures Molecular Machine’s’
Alzheimer’s Disease Consortium Meeting April 7-8
ES-Cat project Kick-off meeting in Cambridge