Revealing the Roles of Subdomains in the Catalytic Behavior of Lipases/Acyltransferases Homologous to CpLIP2 through Rational Design of Chimeric Enzymes

Chembiochem. 2017 May 18;18(10):941-950. doi: 10.1002/cbic.201600672. Epub 2017 May 3.

Abstract

The lipases/acyltransferases homologous to CpLIP2 of Candida parapsilosis efficiently catalyze acyltransfer reactions in lipid/water media with high water activity (aW >0.9). Two new enzymes of this family, CduLAc from Candida dubliniensis and CalLAc8 from Candida albicans, were characterized. Despite 82 % sequence identity, the two enzymes have significant differences in their catalytic behaviors. In order to understand the roles played by the different subdomains of these proteins (main core, cap and C-terminal flap), chimeric enzymes were designed by rational exchange of cap and C-terminal flap, between CduLAc and CalLAc8. The results show that the cap region plays a significant role in substrate specificity; the main core was found to be the most important part of the protein for acyltransfer ability. Similar exchanges were made with CAL-A from Candida antarctica, but only the C-terminal exchange was successful. Yet, the role of this domain was not clearly elucidated, other than that it is essential for activity.

Keywords: cap; enzyme catalysis; lipases/acyltransferases; protein engineering; structure-activity relationships.

MeSH terms

  • Acyltransferases / chemistry
  • Acyltransferases / metabolism*
  • Candida / enzymology*
  • Candida / genetics
  • Catalysis
  • Lipase / chemistry
  • Lipase / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Protein Domains
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Substrate Specificity
  • Water / chemistry

Substances

  • Recombinant Fusion Proteins
  • Water
  • Acyltransferases
  • Lipase