Dedieu_2013_PLoS.One_8_e66913

Reference

Title : Identification of Residues Involved in Substrate Specificity and Cytotoxicity of Two Closely Related Cutinases from Mycobacterium tuberculosis - Dedieu_2013_PLoS.One_8_e66913
Author(s) : Dedieu L , Serveau-Avesque C , Canaan S
Ref : PLoS ONE , 8 :e66913 , 2013
Abstract :

The enzymes belonging to the cutinase family are serine enzymes active on a large panel of substrates such as cutin, triacylglycerols, and phospholipids. In the M. tuberculosis H37Rv genome, seven genes coding for cutinase-like proteins have been identified with strong immunogenic properties suggesting a potential role as vaccine candidates. Two of these enzymes which are secreted and highly homologous, possess distinct substrates specificities. Cfp21 is a lipase and Cut4 is a phospholipase A2, which has cytotoxic effects on macrophages. Structural overlay of their three-dimensional models allowed us to identify three areas involved in the substrate binding process and to shed light on this substrate specificity. By site-directed mutagenesis, residues present in these Cfp21 areas were replaced by residues occurring in Cut4 at the same location. Three mutants acquired phospholipase A1 and A2 activities and the lipase activities of two mutants were 3 and 15 fold greater than the Cfp21 wild type enzyme. In addition, contrary to mutants with enhanced lipase activity, mutants that acquired phospholipase B activities induced macrophage lysis as efficiently as Cut4 which emphasizes the relationship between apparent phospholipase A2 activity and cytotoxicity. Modification of areas involved in substrate specificity, generate recombinant enzymes with higher activity, which may be more immunogenic than the wild type enzymes and could therefore constitute promising candidates for antituberculous vaccine production.

PubMedSearch : Dedieu_2013_PLoS.One_8_e66913
PubMedID: 23843969
Gene_locus related to this paper: myctu-cutas1 , myctu-RV3452

Related information

Substrate PED-A1
Gene_locus myctu-cutas1    myctu-RV3452

Citations formats

Dedieu L, Serveau-Avesque C, Canaan S (2013)
Identification of Residues Involved in Substrate Specificity and Cytotoxicity of Two Closely Related Cutinases from Mycobacterium tuberculosis
PLoS ONE 8 :e66913

Dedieu L, Serveau-Avesque C, Canaan S (2013)
PLoS ONE 8 :e66913