These authors contributed equally to this work.
Understanding the Plasticity of the α/β Hydrolase Fold: Lid Swapping on the Candida antarctica Lipase B Results in Chimeras with Interesting Biocatalytic Properties
Article first published online: 20 JAN 2009
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 10, Issue 3, pages 520–527, February 13, 2009
How to Cite
Skjøt, M., De Maria, L., Chatterjee, R., Svendsen, A., Patkar, S. A., Østergaard, P. R. and Brask, J. (2009), Understanding the Plasticity of the α/β Hydrolase Fold: Lid Swapping on the Candida antarctica Lipase B Results in Chimeras with Interesting Biocatalytic Properties. ChemBioChem, 10: 520–527. doi: 10.1002/cbic.200800668
- Issue published online: 6 FEB 2009
- Article first published online: 20 JAN 2009
- Manuscript Received: 7 OCT 2008
- enzyme catalysis;
- ester hydrolysis;
- gene expression;
- molecular dynamics
The best of both worlds. Long molecular dynamics (MD) simulations of Candida antarctica lipase B (CALB) confirmed the function of helix α5 as a lid structure. Replacement of the helix with corresponding lid regions from CALB homologues from Neurospora crassa and Gibberella zeae resulted in new CALB chimeras with novel biocatalytic properties. The figure shows a snapshot from the MD simulation.
The Candida antarctica lipase B (CALB) has found very extensive use in biocatalysis reactions. Long molecular dynamics simulations of CALB in explicit aqueous solvent confirmed the high mobility of the regions lining the channel that leads into the active site, in particular, of helices α5 and α10. The simulation also confirmed the function of helix α5 as a lid of the lipase. Replacing it with corresponding lid regions from the CALB homologues from Neurospora crassa and Gibberella zeae resulted in two new CALB mutants. Characterization of these revealed several interesting properties, including increased hydrolytic activity on simple esters, specifically substrates with Cα branching on the carboxylic side, and much increased enantioselectivity in hydrolysis of racemic ethyl 2-phenylpropanoate (E>50), which is a common structure of the profen drug family.