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.

Dmitri and Jan to Present at XXVIth Biochemistry Congress
Poster Award for Martin
TA ČR GAMA 2 Grant for Martin
Martin to Present at XXV IUCr 2021
Open Position: Postdoc in Enzymology & Protein Engineering
Open Position: Postdoc in Protein Structural Biology
2nd Hands-on Computational Enzyme Design Course Successfully Behind Us