| Title : Understanding the plasticity of the alpha\/beta hydrolase fold: lid swapping on the Candida antarctica lipase B results in chimeras with interesting biocatalytic properties - Skjot_2009_Chembiochem_10_520 |
| Author(s) : Skjot M , De Maria L , Chatterjee R , Svendsen A , Patkar SA , Ostergaard PR , Brask J |
| Ref : Chembiochem , 10 :520 , 2009 |
| Abstract : The best of both worlds. Long molecular dynamics (MD) simulations of Candida antarctica lipase B (CALB) confirmed the function of helix alpha5 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 alpha5 and alpha10. The simulation also confirmed the function of helix alpha5 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 C(alpha) 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. |
| ESTHER : Skjot_2009_Chembiochem_10_520 |
| PubMedSearch : Skjot_2009_Chembiochem_10_520 |
| PubMedID: 19156649 |
| Gene_locus related to this paper: canar-LipB |
| Gene_locus related to this paper: canar-LipB |
Skjot M, De Maria L, Chatterjee R, Svendsen A, Patkar SA, Ostergaard PR, Brask J (2009)
Understanding the plasticity of the alpha\/beta hydrolase fold: lid swapping on the Candida antarctica lipase B results in chimeras with interesting biocatalytic properties
Chembiochem
10 :520
Skjot M, De Maria L, Chatterjee R, Svendsen A, Patkar SA, Ostergaard PR, Brask J (2009)
Chembiochem
10 :520