Engineering Enzyme Stability and Resistance to an Organic Cosolvent by Modification of Residues in the Access Tunnel

Authors

Koudelakova, T., Chaloupkova, R., Brezovsky, J., Prokop, Z., Sebestova, E., Hesseler, M., Khabiri, M., Plevaka, M., Kulik, D., Kuta Smatanova, I., Rezacova, P., Ettrich, R., Bornscheuer, U. T., Damborsky, J.

Source

ANGEWANDTE CHEMIE INTERNATIONAL EDITION 52: 1959-1963 (2013)

Abstract

Engineering Enzyme Stability and Resistance to Organic Co-solvent by Access Tunnel Modification photo Mutations targeting as few as four residues lining the access tunnel extended enzyme’s half-life in 40% dimethyl sulfoxide from minutes to weeks (4,000-fold) and increased its melting temperature by 19 °C. Protein crystallography and molecular dynamics revealed that the tunnel residue packing is a key determinant of protein stability and the active-site accessibility for co-solvent molecules (red dots). The broad applicability of this concept was verified by analyzing twenty six proteins with buried active sites from all six enzyme classes.

Full text

Citation

Koudelakova, T., Chaloupkova, R., Brezovsky, J., Prokop, Z., Sebestova, E., Hesseler, M., Khabiri, M., Plevaka, M., Kulik, D., Kuta Smatanova, I., Rezacova, P., Ettrich, R., Bornscheuer, U. T., Damborsky, J., 2013: Engineering Enzyme Stability and Resistance to an Organic Cosolvent by Modification of Residues in the Access Tunnel. Angewandte Chemie International Edition 52: 1959-1963.

Jan Stourac won Dean’s Award
Jan Stourac a Master of Science
An article co-authored by our group among the most influential articles of 2016
Martin Toul among the top five in biology/biochemistry category of Sigma-Aldrich competition
Petra Babkova awarded the International Union Crystallography Poster Competition Price
New addition to Loschmidt Laboratories team
Submitted grant proposal to Bill Gates Foundation