Three-dimensional models and structure analysis of corynemycolyltransferases in Corynebacterium glutamicum and Corynebacterium efficiens

The corynemycolyltransferase proteins were identified from Corynebacterium glutamicum and Corynebacterium efficiens genomes using computational tools available in the public domain. Three-dimensional models were constructed for corynemycolyltransferases based on the crystal structures of related mycolyltransferases in Mycobacterium tuberculosis using the comparative modeling methods. The corynemycolyltransferases share overall an alpha/beta-fold characteristic of the mycolyltransferases despite low sequence identity (<20%) shared by some of the corynemycolyltransferases. However, a significant difference is observed in the region between amino acid residues Trp82-Trp97 and Ala222-Asn223 corresponding to mycolyltransferases. The specificity pockets defined by interactions with the trehalose substrate observed in the crystal structure complex of Ag85B mycolyltransferase (PDB code: 1F0P) suggests that trehalose may not bind some corynemycolyltransferases. This is due to critical mutations in corynemycolyltransferase binding subsites that lead to loss of equivalent side-chain interactions with trehalose and unfavorable steric interactions, particularly, in the case of cmytC gene and the protein corresponding to the gene identifier CE0356 with the equivalent Ala222-Asn223 "long insertion loop". Further, the fibronectin binding region (Phe58-Val69), in mycolyltransferases associated with mediating host-pathogen interactions in M. tuberculosis comprises amino acid residue mutations in the corresponding region in the soil bacterium--Corynebacterium corynemycolyltransferases, that suggest a different epitope and therefore possible lack of binding to fibronectin. The corynemycolyltransferase cmytA responsible for the cell shape formation and for maintaining the cell surface integrity is associated with a C-terminal domain that we have recently shown to comprise tandem amino acid sequence repeats that is likely to be associated with a regular secondary structural motif.